Unraveling the role of Xist in X chromosome inactivation: insights from rabbit model and deletion analysis of exons and repeat A.
Academic Journal
|
Publisher: Springer Country of Publication: Switzerland NLM ID: 9705402 Publication Model: Electronic Cited Medium: Internet ISSN: 1420-9071 (Electronic) Linking ISSN: 1420682X NLM ISO Abbreviation: Cell Mol Life Sci Subsets: MEDLINE
Please log in to see more details
Liang M;Zhang L;Lai L;Li Z
Academic Journal
|
Publisher: Springer Country of Publication: Switzerland NLM ID: 9705402 Publication Model: Electronic Cited Medium: Internet ISSN: 1420-9071 (Electronic) Linking ISSN: 1420682X NLM ISO Abbreviation: Cell Mol Life Sci Subsets: MEDLINE
Please log in to see more details
X chromosome inactivation (XCI) is a process that equalizes the expression of X-linked...
more
Unraveling the role of Xist in X chromosome inactivation: insights from rabbit model and deletion analysis of exons and repeat A.
X chromosome inactivation (XCI) is a process that equalizes the expression of X -linked genes between males and females. It relies on Xist, continuously expressed in somatic cells during XCI maintenance. However, how Xist impacts XCI maintenance and its functional motifs remain unclear. In this study, we conducted a comprehensive analysis of Xist, using rabbits as an ideal non-primate model. Homozygous knockout of exon 1, exon 6, and repeat A in female rabbits resulted in embryonic lethality. However, X ∆ReA X females, with intact X chromosome expressing Xist, showed no abnormalities. Interestingly, there were no significant differences between females with homozygous knockout of exons 2-5 and wild-type rabbits, suggesting that exons 2, 3, 4, and 5 are less important for XCI. These findings provide evolutionary insights into Xist function.
(© 2024. The Author(s).)
Publisher: Springer Country of Publication: Switzerland NLM ID: 9705402 Publication Model: Electronic Cited Medium: Internet ISSN: 1420-9071 (Electronic) Linking ISSN: 1420682X NLM ISO Abbreviation: Cell Mol Life Sci Subsets: MEDLINE
(© 2024. The Author(s).)
Subject terms:
Humans - Male - Animals - Rabbits - Female - Chromosomes, Human, X - X Chromosome genetics - Exons genetics - X Chromosome Inactivation genetics - RNA, Long Noncoding geneticsContent provider:
MEDLINE
Check for Full Text
Understanding single-crystal x-ray crystallography / Dennis W. Bennett.
Book
|
2010
Available at Available Merrill-Cazier Books (3rd Floor North) (Call number: QD945 .B46 2010)
close
see all
Items
| Location | Call No. | Status |
|---|---|---|
| Merrill-Cazier Books (3rd Floor North) | QD945 .B46 2010 | Available |
Unmethylated Mosaic Full Mutation Males without Fragile X Syndrome.
Academic Journal
|
Publisher: MDPI Country of Publication: Switzerland NLM ID: 101551097 Publication Model: Electronic Cited Medium: Internet ISSN: 2073-4425 (Electronic) Linking ISSN: 20734425 NLM ISO Abbreviation: Genes (Basel) Subsets: MEDLINE
Please log in to see more details
Tak Y;Schneider A;Santos E;Randol JL;Tassone F;Hagerman P;Hagerman RJ
Academic Journal
|
Publisher: MDPI Country of Publication: Switzerland NLM ID: 101551097 Publication Model: Electronic Cited Medium: Internet ISSN: 2073-4425 (Electronic) Linking ISSN: 20734425 NLM ISO Abbreviation: Genes (Basel) Subsets: MEDLINE
Please log in to see more details
Fragile X syndrome (FXS) is the leading inherited cause of intellectual disability (ID...
more
Unmethylated Mosaic Full Mutation Males without Fragile X Syndrome.
Publisher: MDPI Country of Publication: Switzerland NLM ID: 101551097 Publication Model: Electronic Cited Medium: Internet ISSN: 2073-4425 (Electronic) Linking ISSN: 20734425 NLM ISO Abbreviation: Genes (Basel) Subsets: MEDLINE
Fragile X syndrome (FXS) is the leading inherited cause of intellectual disability (ID) and single gene cause of autism. Although most patients with FXS and the full mutation (FM) have complete methylation of the fragile X messenger ribonucleoprotein 1 ( FMR1 ) gene, some have mosaicism in methylation and/or CGG repeat size, and few have completely unmethylated FM alleles. Those with a complete lack of methylation are rare, with little literature about the cognitive and behavioral phenotypes of these individuals. A review of past literature was conducted regarding individuals with unmethylated and mosaic FMR1 FM. We report three patients with an unmethylated FM FMR1 alleles without any behavioral or cognitive deficits. This is an unusual presentation for men with FM as most patients with an unmethylated FM and no behavioral phenotypes do not receive fragile X DNA testing or a diagnosis of FXS. Our cases showed that mosaic males with unmethylated FMR1 FM alleles may lack behavioral phenotypes due to the presence of smaller alleles producing the FMR1 protein (FMRP). However, these individuals could be at a higher risk of developing fragile X -associated tremor/ataxia syndrome (FXTAS) due to the increased expression of mRNA, similar to those who only have a premutation.
Subject terms:
Male - Humans - DNA Methylation genetics - Fragile X Mental Retardation Protein genetics - Mutation - Fragile X Syndrome genetics - Fragile X Syndrome complications - Ataxia - TremorContent provider:
MEDLINE
SpringerLink An electronic book accessible through the World Wide Web; click for information
FMR1 Carriers Report Executive Function Changes Prior to Fragile X -Associated Tremor/Ataxia Syndrome: A Longitudinal Study.
Academic Journal
|
Publisher: Wiley-Liss Country of Publication: United States NLM ID: 8610688 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1531-8257 (Electronic) Linking ISSN: 08853185 NLM ISO Abbreviation: Mov Disord Subsets: MEDLINE
Please log in to see more details
Hessl D;Mandujano Rojas K;Ferrer E;Espinal G;Famula J;Schneider A;Hagerman ...
Academic Journal
|
Publisher: Wiley-Liss Country of Publication: United States NLM ID: 8610688 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1531-8257 (Electronic) Linking ISSN: 08853185 NLM ISO Abbreviation: Mov Disord Subsets: MEDLINE
Please log in to see more details
Background: Men with fragile X-associated tremor/ataxia syndrome (FXTAS) often develop...
more
FMR1 Carriers Report Executive Function Changes Prior to Fragile X -Associated Tremor/Ataxia Syndrome: A Longitudinal Study.
Publisher: Wiley-Liss Country of Publication: United States NLM ID: 8610688 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1531-8257 (Electronic) Linking ISSN: 08853185 NLM ISO Abbreviation: Mov Disord Subsets: MEDLINE
Background: Men with fragile X -associated tremor/ataxia syndrome (FXTAS) often develop executive dysfunction, characterized by disinhibition, frontal dyscontrol of movement, and working memory and attention changes. Although cross-sectional studies have suggested that earlier executive function changes may precede FXTAS, the lack of longitudinal studies has made it difficult to address this hypothesis.
Objective: To determine whether executive function deterioration experienced by premutation carriers (PC) in daily life precedes and predicts FXTAS.
Methods: This study included 66 FMR1 PC ranging from 40 to 78 years (mean, 59.5) and 31 well-matched healthy controls (HC) ages 40 to 75 (mean, 57.7) at baseline. Eighty-four participants returned for 2 to 5 follow up visits over a duration of 1 to 9 years (mean, 4.6); 28 of the PC developed FXTAS. The Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A) was completed by participants and their spouses/partners at each visit.
Results: Longitudinal mixed model regression analyses showed a greater decline with age in PC compared to HC on the Metacognition Index (MI; self-initiation, working memory, organization, task monitoring). Conversion to FXTAS was associated with worsening MI and Behavioral Regulation Index (BRI; inhibition, flexibility, emotion modulation). For spouse/partner report, FXTAS conversion was associated with worsening MI. Finally, increased self-report executive function problems at baseline significantly predicted later development of FXTAS.
Conclusions: Executive function changes experienced by male PC represent a prodrome of the later movement disorder. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
(© 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)
Objective: To determine whether executive function deterioration experienced by premutation carriers (PC) in daily life precedes and predicts FXTAS.
Methods: This study included 66 FMR1 PC ranging from 40 to 78 years (mean, 59.5) and 31 well-matched healthy controls (HC) ages 40 to 75 (mean, 57.7) at baseline. Eighty-four participants returned for 2 to 5 follow up visits over a duration of 1 to 9 years (mean, 4.6); 28 of the PC developed FXTAS. The Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A) was completed by participants and their spouses/partners at each visit.
Results: Longitudinal mixed model regression analyses showed a greater decline with age in PC compared to HC on the Metacognition Index (MI; self-initiation, working memory, organization, task monitoring). Conversion to FXTAS was associated with worsening MI and Behavioral Regulation Index (BRI; inhibition, flexibility, emotion modulation). For spouse/partner report, FXTAS conversion was associated with worsening MI. Finally, increased self-report executive function problems at baseline significantly predicted later development of FXTAS.
Conclusions: Executive function changes experienced by male PC represent a prodrome of the later movement disorder. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
(© 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)
Subject terms:
Adult - Humans - Male - Executive Function physiology - Tremor - Longitudinal Studies - Cross-Sectional Studies - Fragile X Mental Retardation Protein genetics - Ataxia - Fragile X Syndrome genetics - Fragile X Syndrome complications - Movement Disorders complicationsContent provider:
MEDLINE
Cochlear Nucleus Transcriptome of a Fragile X Mouse Model Reveals Candidate Genes for Hyperacusis.
Academic Journal
|
Publisher: Wiley-Blackwell Country of Publication: United States NLM ID: 8607378 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1531-4995 (Electronic) Linking ISSN: 0023852X NLM ISO Abbreviation: Laryngoscope Subsets: MEDLINE
Please log in to see more details
Sakano H;Castle MS;Kundu P
Academic Journal
|
Publisher: Wiley-Blackwell Country of Publication: United States NLM ID: 8607378 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1531-4995 (Electronic) Linking ISSN: 0023852X NLM ISO Abbreviation: Laryngoscope Subsets: MEDLINE
Please log in to see more details
Objective: Fragile X Syndrome (FXS) is a hereditary form of autism spectrum disorder. ...
more
Cochlear Nucleus Transcriptome of a Fragile X Mouse Model Reveals Candidate Genes for Hyperacusis.
Publisher: Wiley-Blackwell Country of Publication: United States NLM ID: 8607378 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1531-4995 (Electronic) Linking ISSN: 0023852X NLM ISO Abbreviation: Laryngoscope Subsets: MEDLINE
Objective: Fragile X Syndrome (FXS) is a hereditary form of autism spectrum disorder. It is caused by a trinucleotide repeat expansion in the Fmr1 gene, leading to a loss of Fragile X Protein (FMRP) expression. The loss of FMRP causes auditory hypersensitivity: FXS patients display hyperacusis and the Fmr1- knock-out (KO) mouse model for FXS exhibits auditory seizures. FMRP is strongly expressed in the cochlear nucleus and other auditory brainstem nuclei. We hypothesize that the Fmr1-KO mouse has altered gene expression in the cochlear nucleus that may contribute to auditory hypersensitivity.
Methods: RNA was isolated from cochlear nuclei of Fmr1-KO and WT mice. Using next-generation sequencing (RNA-seq), the transcriptomes of Fmr1-KO mice and WT mice (n = 3 each) were compared and analyzed using gene ontology programs.
Results: We identified 270 unique, differentially expressed genes between Fmr1-KO and WT cochlear nuclei. Upregulated genes (67%) are enriched in those encoding secreted molecules. Downregulated genes (33%) are enriched in neuronal function, including synaptic pathways, some of which are ideal candidate genes that may contribute to hyperacusis.
Conclusion: The loss of FMRP can affect the expression of genes in the cochlear nucleus that are important for neuronal signaling. One of these, Kcnab2, which encodes a subunit of the Shaker voltage-gated potassium channel, is expressed at an abnormally low level in the Fmr1-KO cochlear nucleus. Kcnab2 and other differentially expressed genes may represent pathways for the development of hyperacusis. Future studies will be aimed at investigating the effects of these altered genes on hyperacusis.
Level of Evidence: N/A Laryngoscope, 134:1363-1371, 2024.
(© 2023 The American Laryngological, Rhinological and Otological Society, Inc.)
Methods: RNA was isolated from cochlear nuclei of Fmr1-KO and WT mice. Using next-generation sequencing (RNA-seq), the transcriptomes of Fmr1-KO mice and WT mice (n = 3 each) were compared and analyzed using gene ontology programs.
Results: We identified 270 unique, differentially expressed genes between Fmr1-KO and WT cochlear nuclei. Upregulated genes (67%) are enriched in those encoding secreted molecules. Downregulated genes (33%) are enriched in neuronal function, including synaptic pathways, some of which are ideal candidate genes that may contribute to hyperacusis.
Conclusion: The loss of FMRP can affect the expression of genes in the cochlear nucleus that are important for neuronal signaling. One of these, Kcnab2, which encodes a subunit of the Shaker voltage-gated potassium channel, is expressed at an abnormally low level in the Fmr1-KO cochlear nucleus. Kcnab2 and other differentially expressed genes may represent pathways for the development of hyperacusis. Future studies will be aimed at investigating the effects of these altered genes on hyperacusis.
Level of Evidence: N/A Laryngoscope, 134:1363-1371, 2024.
(© 2023 The American Laryngological, Rhinological and Otological Society, Inc.)
Subject terms:
Humans - Mice - Animals - Hyperacusis genetics - Transcriptome - Fragile X Mental Retardation Protein genetics - Fragile X Mental Retardation Protein metabolism - Mice, Knockout - Disease Models, Animal - Shaker Superfamily of Potassium Channels genetics - Shaker Superfamily of Potassium Channels metabolism - Cochlear Nucleus metabolism - Autism Spectrum Disorder - Fragile X Syndrome genetics - Fragile X Syndrome metabolismContent provider:
MEDLINE
Structure determination by X-ray crystallography / M.F.C. Ladd and R.A. Palmer.
Book
|
1993
Available at Available Merrill-Cazier Books (3rd Floor North) (Call number: QD945 .L32 1993)
close
see all
Items
| Location | Call No. | Status |
|---|---|---|
| Merrill-Cazier Books (3rd Floor North) | QD945 .L32 1993 | Available |
Altered brain serotonin 5-HT 1A receptor expression and function in juvenile Fmr1 knockout mice.
Academic Journal
|
Publisher: Pergamon Press Country of Publication: England NLM ID: 0236217 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-7064 (Electronic) Linking ISSN: 00283908 NLM ISO Abbreviation: Neuropharmacology Subsets: MEDLINE
Please log in to see more details
Saraf TS;Chen Y;Tyagi R;Canal CE
Academic Journal
|
Publisher: Pergamon Press Country of Publication: England NLM ID: 0236217 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-7064 (Electronic) Linking ISSN: 00283908 NLM ISO Abbreviation: Neuropharmacology Subsets: MEDLINE
Please log in to see more details
There are no approved pharmacotherapies for fragile X syndrome (FXS), a rare neurodeve...
more
Altered brain serotonin 5-HT 1A receptor expression and function in juvenile Fmr1 knockout mice.
Publisher: Pergamon Press Country of Publication: England NLM ID: 0236217 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-7064 (Electronic) Linking ISSN: 00283908 NLM ISO Abbreviation: Neuropharmacology Subsets: MEDLINE
There are no approved pharmacotherapies for fragile X syndrome (FXS), a rare neurodevelopmental disorder caused by a mutation in the FMR1 promoter region that leads to various symptoms, including intellectual disability and auditory hypersensitivity. The gene that encodes inhibitory serotonin 1A receptors (5-HT 1A Rs) is differentially expressed in embryonic brain tissue from individuals with FXS, and 5-HT 1A Rs are highly expressed in neural systems that are disordered in FXS, providing a rationale to focus on 5-HT 1A Rs as targets to treat symptoms of FXS. We examined agonist-labeled 5-HT 1A R densities in male and female Fmr1 knockout mice and found no differences in whole-brain 5-HT 1A R expression in adult control compared to Fmr1 knockout mice. However, juvenile Fmr1 knockout mice had lower whole-brain 5-HT 1A R expression than age-matched controls. Consistent with these results, juvenile Fmr1 knockout mice showed reduced behavioral responses elicited by the 5-HT 1A R agonist (R)-8-OH-DPAT, effects blocked by the selective 5-HT 1A R antagonist, WAY-100635. Also, treatment with the selective 5-HT 1A R agonist, NLX-112, dose-dependently prevented audiogenic seizures (AGS) in juvenile Fmr1 knockout mice, an effect reversed by WAY-100635. Suggestive of a potential role for 5-HT 1A Rs in regulating AGS, compared to males, female Fmr1 knockout mice had a lower prevalence of AGS and higher expression of antagonist-labeled 5-HT 1A Rs in the inferior colliculus and auditory cortex. These results provide preclinical support that 5-HT 1A R agonists may be therapeutic for young individuals with FXS hypersensitive to auditory stimuli.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023. Published by Elsevier Ltd.)
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023. Published by Elsevier Ltd.)
Subject terms:
Animals - Female - Male - Mice - Fragile X Mental Retardation Protein genetics - Fragile X Mental Retardation Protein metabolism - Mice, Knockout - Receptor, Serotonin, 5-HT1A genetics - Receptor, Serotonin, 5-HT1A metabolism - Serotonin - Epilepsy, Reflex - Fragile X Syndrome drug therapy - Fragile X Syndrome genetics - Fragile X Syndrome metabolism - Inferior Colliculi metabolismContent provider:
MEDLINE
Use of X-ray crystallography in the design of antiviral agents / edited by W.G. Laver, Gillian Air.
Book
|
1990
Available at Available Merrill-Cazier Books (3rd Floor North) (Call number: RS431 .A66U74 1990)
close
see all
Items
| Location | Call No. | Status |
|---|---|---|
| Merrill-Cazier Books (3rd Floor North) | RS431 .A66U74 1990 | Available |
The NSP3 protein of SARS-CoV-2 binds fragile X mental retardation proteins to disrupt UBAP2L interactions.
Academic Journal
|
Publisher: Nature Publishing Group Country of Publication: England NLM ID: 100963049 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1469-3178 (Electronic) Linking ISSN: 1469221X NLM ISO Abbreviation: EMBO Rep Subsets: MEDLINE
Please log in to see more details
Garvanska DH;Alvarado RE;Mundt FO;Lindqvist R;Duel JK;Coscia F;Nilsson E;Lo...
Academic Journal
|
Publisher: Nature Publishing Group Country of Publication: England NLM ID: 100963049 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1469-3178 (Electronic) Linking ISSN: 1469221X NLM ISO Abbreviation: EMBO Rep Subsets: MEDLINE
Please log in to see more details
Viruses interact with numerous host factors to facilitate viral replication and to dam...
more
The NSP3 protein of SARS-CoV-2 binds fragile X mental retardation proteins to disrupt UBAP2L interactions.
Publisher: Nature Publishing Group Country of Publication: England NLM ID: 100963049 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1469-3178 (Electronic) Linking ISSN: 1469221X NLM ISO Abbreviation: EMBO Rep Subsets: MEDLINE
Viruses interact with numerous host factors to facilitate viral replication and to dampen antiviral defense mechanisms. We currently have a limited mechanistic understanding of how SARS-CoV-2 binds host factors and the functional role of these interactions. Here, we uncover a novel interaction between the viral NSP3 protein and the fragile X mental retardation proteins (FMRPs: FMR1, FXR1-2). SARS-CoV-2 NSP3 mutant viruses preventing FMRP binding have attenuated replication in vitro and reduced levels of viral antigen in lungs during the early stages of infection. We show that a unique peptide motif in NSP3 binds directly to the two central KH domains of FMRPs and that this interaction is disrupted by the I304N mutation found in a patient with fragile X syndrome. NSP3 binding to FMRPs disrupts their interaction with the stress granule component UBAP2L through direct competition with a peptide motif in UBAP2L to prevent FMRP incorporation into stress granules. Collectively, our results provide novel insight into how SARS-CoV-2 hijacks host cell proteins and provides molecular insight into the possible underlying molecular defects in fragile X syndrome.
(© 2024. The Author(s).)
(© 2024. The Author(s).)
Subject terms:
Humans - Fragile X Mental Retardation Protein genetics - Fragile X Mental Retardation Protein metabolism - Peptides metabolism - RNA-Binding Proteins genetics - SARS-CoV-2 - COVID-19 - Fragile X Syndrome genetics - Fragile X Syndrome metabolismContent provider:
MEDLINE
Structure determination by X-ray crystallography / M. F. C. Ladd and R. A. Palmer.
Book
|
1977
Available at Available Merrill-Cazier BARN, Books, Circulation Desk (1st Floor) (Call number: QD 945 .L32)
close
see all
Items
| Location | Call No. | Status |
|---|---|---|
| Merrill-Cazier BARN, Books, Circulation Desk (1st Floor) | QD 945 .L32 | Available |
Request from BARN -- YOUR NAME is REQUIRED to process request.
Imprinted X chromosome inactivation at the gamete-to-embryo transition.
Academic Journal
|
Publisher: Cell Press Country of Publication: United States NLM ID: 9802571 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1097-4164 (Electronic) Linking ISSN: 10972765 NLM ISO Abbreviation: Mol Cell Subsets: MEDLINE
Please log in to see more details
Wei C;Kesner B;Yin H;Lee JT
Academic Journal
|
Publisher: Cell Press Country of Publication: United States NLM ID: 9802571 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1097-4164 (Electronic) Linking ISSN: 10972765 NLM ISO Abbreviation: Mol Cell Subsets: MEDLINE
Please log in to see more details
In mammals, dosage compensation involves two parallel processes: (1) X inactivation, w...
more
Imprinted X chromosome inactivation at the gamete-to-embryo transition.
Publisher: Cell Press Country of Publication: United States NLM ID: 9802571 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1097-4164 (Electronic) Linking ISSN: 10972765 NLM ISO Abbreviation: Mol Cell Subsets: MEDLINE
In mammals, dosage compensation involves two parallel processes: (1) X inactivation, which equalizes X chromosome dosage between males and females, and (2) X hyperactivation, which upregulates the active X for X -autosome balance. The field currently favors models whereby dosage compensation initiates "de novo" during mouse development. Here, we develop "So-Smart-seq" to revisit the question and interrogate a comprehensive transcriptome including noncoding genes and repeats in mice. Intriguingly, de novo silencing pertains only to a subset of Xp genes. Evolutionarily older genes and repetitive elements demonstrate constitutive Xp silencing, adopt distinct signatures, and do not require Xist to initiate silencing. We trace Xp silencing backward in developmental time to meiotic sex chromosome inactivation in the male germ line and observe that Xm hyperactivation is timed to Xp silencing on a gene-by-gene basis. Thus, during the gamete-to-embryo transition, older Xp genes are transmitted in a "pre-inactivated" state. These findings have implications for the evolution of imprinting.
Competing Interests: Declaration of interests J.T.L. is a cofounder of Fulcrum Therapeutics and an advisor to Skyhawk Therapeutics.
(Copyright © 2024 Elsevier Inc. All rights reserved.)
Competing Interests: Declaration of interests J.T.L. is a cofounder of Fulcrum Therapeutics and an advisor to Skyhawk Therapeutics.
(Copyright © 2024 Elsevier Inc. All rights reserved.)
Subject terms:
Female - Mice - Male - Animals - Genomic Imprinting - Germ Cells - Epigenesis, Genetic - Embryo, Mammalian - X Chromosome genetics - Mammals genetics - X Chromosome Inactivation genetics - RNA, Long Noncoding geneticsContent provider:
MEDLINE
Elements of X-ray crystallography [by] Leonid V. Azároff.
Book
|
1968
Available at Available Merrill-Cazier Books (3rd Floor North) (Call number: QD945 .A85)
Mitochondrial dysfunction in Fragile X syndrome and Fragile X -associated tremor/ataxia syndrome: prospect use of antioxidants and mitochondrial nutrients.
Academic Journal
|
Publisher: Reidel Country of Publication: Netherlands NLM ID: 0403234 Publication Model: Electronic Cited Medium: Internet ISSN: 1573-4978 (Electronic) Linking ISSN: 03014851 NLM ISO Abbreviation: Mol Biol Rep Subsets: MEDLINE
Please log in to see more details
Pagano G;Lyakhovich A;Pallardó FV;Tiano L;Zatterale A;Trifuoggi M
Academic Journal
|
Publisher: Reidel Country of Publication: Netherlands NLM ID: 0403234 Publication Model: Electronic Cited Medium: Internet ISSN: 1573-4978 (Electronic) Linking ISSN: 03014851 NLM ISO Abbreviation: Mol Biol Rep Subsets: MEDLINE
Please log in to see more details
Fragile X syndrome (FXS) is a genetic disorder characterized by mutation in the FMR1 g...
more
Mitochondrial dysfunction in Fragile X syndrome and Fragile X -associated tremor/ataxia syndrome: prospect use of antioxidants and mitochondrial nutrients.
Publisher: Reidel Country of Publication: Netherlands NLM ID: 0403234 Publication Model: Electronic Cited Medium: Internet ISSN: 1573-4978 (Electronic) Linking ISSN: 03014851 NLM ISO Abbreviation: Mol Biol Rep Subsets: MEDLINE
Fragile X syndrome (FXS) is a genetic disorder characterized by mutation in the FMR1 gene, leading to the absence or reduced levels of fragile X Messenger Ribonucleoprotein 1 (FMRP). This results in neurodevelopmental deficits, including autistic spectrum conditions. On the other hand, Fragile X -associated tremor/ataxia syndrome (FXTAS) is a distinct disorder caused by the premutation in the FMR1 gene. FXTAS is associated with elevated levels of FMR1 mRNA, leading to neurodegenerative manifestations such as tremors and ataxia.Mounting evidence suggests a link between both syndromes and mitochondrial dysfunction (MDF). In this minireview, we critically examine the intricate relationship between FXS, FXTAS, and MDF, focusing on potential therapeutic avenues to counteract or mitigate their adverse effects. Specifically, we explore the role of mitochondrial cofactors and antioxidants, with a particular emphasis on alpha-lipoic acid (ALA), carnitine (CARN) and Coenzyme Q10 (CoQ10). Findings from this review will contribute to a deeper understanding of these disorders and foster novel therapeutic strategies to enhance patient outcomes.
(© 2024. The Author(s).)
(© 2024. The Author(s).)
Subject terms:
Humans - Tremor drug therapy - Tremor genetics - Antioxidants therapeutic use - Ataxia drug therapy - Ataxia genetics - Fragile X Mental Retardation Protein genetics - Fragile X Syndrome drug therapy - Fragile X Syndrome genetics - Mitochondrial DiseasesContent provider:
MEDLINE
The precession method in X-ray crystallography [by] Martin J. Buerger.
Book
|
1964
Available at Available Merrill-Cazier Books (3rd Floor North) (Call number: QD945 .B79)
Developmental Impairments of Synaptic Refinement in the Thalamus of a Mouse Model of Fragile X Syndrome.
Academic Journal
|
Publisher: Springer Singapore Country of Publication: Singapore NLM ID: 101256850 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1995-8218 (Electronic) Linking ISSN: 19958218 NLM ISO Abbreviation: Neurosci Bull Subsets: MEDLINE
Please log in to see more details
Wu X;Liu Y;Wang X;Zheng L;Pan L;Wang H
Academic Journal
|
Publisher: Springer Singapore Country of Publication: Singapore NLM ID: 101256850 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1995-8218 (Electronic) Linking ISSN: 19958218 NLM ISO Abbreviation: Neurosci Bull Subsets: MEDLINE
Please log in to see more details
While somatosensory over-reactivity is a common feature of autism spectrum disorders s...
more
Developmental Impairments of Synaptic Refinement in the Thalamus of a Mouse Model of Fragile X Syndrome.
Publisher: Springer Singapore Country of Publication: Singapore NLM ID: 101256850 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1995-8218 (Electronic) Linking ISSN: 19958218 NLM ISO Abbreviation: Neurosci Bull Subsets: MEDLINE
While somatosensory over-reactivity is a common feature of autism spectrum disorders such as fragile X syndrome (FXS), the thalamic mechanisms underlying this remain unclear. Here, we found that the developmental elimination of synapses formed between the principal nucleus of V (PrV) and the ventral posterior medial nucleus (VPm) of the somatosensory system was delayed in fragile X mental retardation 1 gene knockout (Fmr1 KO) mice, while the developmental strengthening of these synapses was disrupted. Immunohistochemistry showed excessive VGluT2 puncta in mutants at P12-13, but not at P7-8 or P15-16, confirming a delay in somatic pruning of PrV-VPm synapses. Impaired synaptic function was associated with a reduction in the frequency of quantal AMPA events, as well as developmental deficits in presynaptic vesicle size and density. Our results uncovered the developmental impairment of thalamic relay synapses in Fmr1 KO mice and suggest that a thalamic contribution to the somatosensory over-reactivity in FXS should be considered.
(© 2023. The Author(s).)
(© 2023. The Author(s).)
Subject terms:
Mice - Animals - Mice, Knockout - Disease Models, Animal - Thalamus metabolism - Synapses metabolism - Fragile X Mental Retardation Protein genetics - Fragile X Mental Retardation Protein metabolism - Fragile X Syndrome genetics - Autism Spectrum DisorderContent provider:
MEDLINE
The powder method in X-ray crystallography [by] Leonid V. Azároff [and] Martin J. Buerger.
Book
|
1958
Available at Available Merrill-Cazier Books (3rd Floor North) (Call number: QD945 .A9)
Variation of FMRP Expression in Peripheral Blood Mononuclear Cells from Individuals with Fragile X Syndrome.
Academic Journal
|
Publisher: MDPI Country of Publication: Switzerland NLM ID: 101551097 Publication Model: Electronic Cited Medium: Internet ISSN: 2073-4425 (Electronic) Linking ISSN: 20734425 NLM ISO Abbreviation: Genes (Basel) Subsets: MEDLINE
Please log in to see more details
Randol JL;Kim K;Ponzini MD;Tassone F;Falcon AK;Hagerman RJ;Hagerman PJ
Academic Journal
|
Publisher: MDPI Country of Publication: Switzerland NLM ID: 101551097 Publication Model: Electronic Cited Medium: Internet ISSN: 2073-4425 (Electronic) Linking ISSN: 20734425 NLM ISO Abbreviation: Genes (Basel) Subsets: MEDLINE
Please log in to see more details
Fragile X syndrome (FXS) is the most common heritable cause of intellectual disability...
more
Variation of FMRP Expression in Peripheral Blood Mononuclear Cells from Individuals with Fragile X Syndrome.
Publisher: MDPI Country of Publication: Switzerland NLM ID: 101551097 Publication Model: Electronic Cited Medium: Internet ISSN: 2073-4425 (Electronic) Linking ISSN: 20734425 NLM ISO Abbreviation: Genes (Basel) Subsets: MEDLINE
Fragile X syndrome (FXS) is the most common heritable cause of intellectual disability and autism spectrum disorder. The syndrome is often caused by greatly reduced or absent protein expression from the fragile X messenger ribonucleoprotein 1 ( FMR1 ) gene due to expansion of a 5'-non-coding trinucleotide (CGG) element beyond 200 repeats (full mutation). To better understand the complex relationships among FMR1 allelotype, methylation status, mRNA expression, and FMR1 protein (FMRP) levels, FMRP was quantified in peripheral blood mononuclear cells for a large cohort of FXS ( n = 154) and control ( n = 139) individuals using time-resolved fluorescence resonance energy transfer. Considerable size and methylation mosaicism were observed among individuals with FXS, with FMRP detected only in the presence of such mosaicism. No sample with a minimum allele size greater than 273 CGG repeats had significant levels of FMRP. Additionally, an association was observed between FMR1 mRNA and FMRP levels in FXS samples, predominantly driven by those with the lowest FMRP values. This study underscores the complexity of FMR1 allelotypes and FMRP expression and prompts a reevaluation of FXS therapies aimed at reactivating large full mutation alleles that are likely not capable of producing sufficient FMRP to improve cognitive function.
Subject terms:
Humans - Trinucleotide Repeat Expansion genetics - Leukocytes, Mononuclear metabolism - Fragile X Mental Retardation Protein genetics - Fragile X Mental Retardation Protein metabolism - RNA, Messenger genetics - RNA, Messenger metabolism - Fragile X Syndrome genetics - Autism Spectrum Disorder geneticsContent provider:
MEDLINE
X-PLOR : version 3.1 : a system for x-ray crystallography and NMR / Axel T. Brünger.
Book
|
1992
Available at Available Merrill-Cazier Books (3rd Floor North) (Call number: QD945 .B786 1992)
close
see all
Items
| Location | Call No. | Status |
|---|---|---|
| Merrill-Cazier Books (3rd Floor North) | QD945 .B786 1992 | Available |
Challenges in developing therapies in fragile X syndrome: how the FXLEARN trial can guide research.
Academic Journal
|
Publisher: American Society for Clinical Investigation Country of Publication: United States NLM ID: 7802877 Publication Model: Electronic Cited Medium: Internet ISSN: 1558-8238 (Electronic) Linking ISSN: 00219738 NLM ISO Abbreviation: J Clin Invest Subsets: MEDLINE
Please log in to see more details
Neul JL
Academic Journal
|
Publisher: American Society for Clinical Investigation Country of Publication: United States NLM ID: 7802877 Publication Model: Electronic Cited Medium: Internet ISSN: 1558-8238 (Electronic) Linking ISSN: 00219738 NLM ISO Abbreviation: J Clin Invest Subsets: MEDLINE
Please log in to see more details
Fragile X syndrome (FXS), the most common inherited cause of intellectual disability a...
more
Challenges in developing therapies in fragile X syndrome: how the FXLEARN trial can guide research.
Publisher: American Society for Clinical Investigation Country of Publication: United States NLM ID: 7802877 Publication Model: Electronic Cited Medium: Internet ISSN: 1558-8238 (Electronic) Linking ISSN: 00219738 NLM ISO Abbreviation: J Clin Invest Subsets: MEDLINE
Fragile X syndrome (FXS), the most common inherited cause of intellectual disability and the single-gene cause of autism, is caused by decreased expression of the fragile X messenger ribonucleoprotein protein (FMRP), a ribosomal-associated RNA-binding protein involved in translational repression. Extensive preclinical work in several FXS animal models supported the therapeutic potential of decreasing metabotropic glutamate receptor (mGluR) signaling to correct translation of proteins related to synaptic plasticity; however, multiple clinical trials failed to show conclusive evidence of efficacy. In this issue of the JCI, Berry-Kravis and colleagues conducted the FXLEARN clinical trial to address experimental design concerns from previous trials. Unfortunately, despite treatment of young children with combined pharmacological and learning interventions for a prolonged period, no efficacy of blocking mGluR activity was observed. Future systematic evaluation of potential therapeutic approaches should evaluate consistency between human and animal pathophysiological mechanisms, utilize innovative clinical trial design from FXLEARN, and incorporate translatable biomarkers.
Subject terms:
Animals - Child - Humans - Child, Preschool - Fragile X Mental Retardation Protein genetics - Fragile X Mental Retardation Protein metabolism - Fragile X Mental Retardation Protein therapeutic use - Neuronal Plasticity - Fragile X Syndrome drug therapy - Fragile X Syndrome genetics - Intellectual Disability - Receptors, Metabotropic Glutamate genetics - Receptors, Metabotropic Glutamate metabolismContent provider:
MEDLINE
Chemical crystallography; an introduction to optical and X-ray methods.
Book
|
1961
Available at Available Merrill-Cazier Books (3rd Floor North) (Call number: QD951 .B77 1961)
close
see all
Items
| Location | Call No. | Status |
|---|---|---|
| Merrill-Cazier Books (3rd Floor North) | QD951 .B77 1961 | Available |
mGluR7 allosteric modulator AMN082 corrects protein synthesis and pathological phenotypes in FXS.
Academic Journal
|
Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101487380 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1757-4684 (Electronic) Linking ISSN: 17574676 NLM ISO Abbreviation: EMBO Mol Med Subsets: MEDLINE
Please log in to see more details
Kumar V;Lee KY;Acharya A;Babik MS;Christian-Hinman CA;Rhodes JS;Tsai NP
Academic Journal
|
Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101487380 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1757-4684 (Electronic) Linking ISSN: 17574676 NLM ISO Abbreviation: EMBO Mol Med Subsets: MEDLINE
Please log in to see more details
Fragile X syndrome (FXS) is the leading cause of inherited autism and intellectual dis...
more
mGluR7 allosteric modulator AMN082 corrects protein synthesis and pathological phenotypes in FXS.
Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101487380 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1757-4684 (Electronic) Linking ISSN: 17574676 NLM ISO Abbreviation: EMBO Mol Med Subsets: MEDLINE
Fragile X syndrome (FXS) is the leading cause of inherited autism and intellectual disabilities. Aberrant protein synthesis due to the loss of fragile X messenger ribonucleoprotein (FMRP) is the major defect in FXS, leading to a plethora of cellular and behavioral abnormalities. However, no treatments are available to date. In this study, we found that activation of metabotropic glutamate receptor 7 (mGluR7) using a positive allosteric modulator named AMN082 represses protein synthesis through ERK1/2 and eIF4E signaling in an FMRP-independent manner. We further demonstrated that treatment of AMN082 leads to a reduction in neuronal excitability, which in turn ameliorates audiogenic seizure susceptibility in Fmr1 KO mice, the FXS mouse model. When evaluating the animals' behavior, we showed that treatment of AMN082 reduces repetitive behavior and improves learning and memory in Fmr1 KO mice. This study uncovers novel functions of mGluR7 and AMN082 and suggests the activation of mGluR7 as a potential therapeutic approach for treating FXS.
(© 2024. The Author(s).)
(© 2024. The Author(s).)
