Abstract:
:During postnatal development, neuronal activity controls the remodeling of initially imprecise neuronal connections through the regulation of gene expression. MeCP2 binds to methylated DNA and modulates gene expression during neuronal development and MECP2 mutation causes the autistic disorder Rett syndrome. To investigate a role for MeCP2 in neuronal circuit refinement and to identify activity-dependent MeCP2 transcription regulations, we leveraged the precise organization and accessibility of olfactory sensory axons to manipulation of neuronal activity through odorant exposure in vivo. We demonstrate that olfactory sensory axons failed to develop complete convergence when Mecp2 is deficient in olfactory sensory neurons (OSNs) in an otherwise wild-type animal. Furthermore, we demonstrate that expression of selected adhesion genes was elevated in Mecp2-deficient glomeruli, while acute odor stimulation in control mice resulted in significantly reduced MeCP2 binding to these gene loci, correlating with increased expression. Thus, MeCP2 is required for both circuitry refinement and activity-dependent transcriptional responses in OSNs.
journal_name
Hum Mol Genetjournal_title
Human molecular geneticsauthors
Lee W,Yun JM,Woods R,Dunaway K,Yasui DH,Lasalle JM,Gong Qdoi
10.1093/hmg/ddu358subject
Has Abstractpub_date
2014-12-01 00:00:00pages
6366-74issue
23eissn
0964-6906issn
1460-2083pii
ddu358journal_volume
23pub_type
杂志文章abstract::We, amongst others, have shown that CC homozygosity at the -22C>T promoter polymorphism in presenilin 1 (PSEN1) is associated with increased risk for Alzheimer's disease (AD). Also, studies in AD brains suggested that CC homozygosity increased the risk for AD by increasing the Abeta load. We characterized the PSEN1 pr...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddg098
更新日期:2003-04-15 00:00:00
abstract::Gene therapy holds great promise for curing Duchenne muscular dystrophy (DMD), the most common fatal inherited childhood muscle disease. Success of DMD gene therapy depends upon functional improvement in both skeletal and cardiac muscle. Numerous gene transfer studies have been performed to correct skeletal muscle pat...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddh174
更新日期:2004-08-01 00:00:00
abstract::While several high-resolution recombination maps exist for European-descent populations, the recombination landscape of African populations remains relatively understudied. Given that there is high genetic divergence among groups in Africa, it is possible that recombination hotspots also diverge significantly. Both li...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddab020
更新日期:2021-01-14 00:00:00
abstract::Interpretation of genetic association results is difficult because signals often lack biological context. To generate hypotheses of the functional genetic etiology of complex cardiometabolic traits, we estimated the genetically determined component of gene expression from common variants using PrediXcan (1) and determ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddy435
更新日期:2019-04-01 00:00:00
abstract::Losing of ovarian functions prior to natural menopause age causes female infertility and early menopause. Premature ovarian insufficiency (POI) is defined as the loss of ovarian activity before 40 years of age. Known genetic causes account for 25-30% of POI cases, demonstrating the high genetic heterogeneity of POI an...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddaa153
更新日期:2020-09-29 00:00:00
abstract::The autosomal recessive mouse mutation retinal degeneration 6 (rd6) causes small, white retinal spots and progressive photoreceptor degeneration similar to that observed in human flecked retinal diseases. Using a positional cloning approach, we determined that rd6 mice carry a splice donor mutation in the mouse homolo...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/11.16.1879
更新日期:2002-08-01 00:00:00
abstract::Beside the well-known polyglutamine expansions involved in several neurodegenerative disorders, convergent recent findings pointed to the expansion of polyalanine stretches as a disease mechanism in congenital malformations, skeletal dysplasia and nervous system anomalies. Polyalanine stretches have been predicted in ...
journal_title:Human molecular genetics
pub_type: 杂志文章,评审
doi:10.1093/hmg/ddh251
更新日期:2004-10-01 00:00:00
abstract::The breast cancer gene, BRCA2, is essential for viability, yet patients with Fanconi anemia-D1 subtype are born alive with biallelic mutations in this gene. The hypomorphic nature of the mutations is believed to support viability, but this is not always apparent. One such mutation is IVS7+2T>G, which causes premature ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddw066
更新日期:2016-05-15 00:00:00
abstract::The contribution of BRCA1 and BRCA2 to familial and non-familial forms of breast cancer has been difficult to accurately estimate because of the myriad of potential genetic and epigenetic mechanisms that can ultimately influence their expression and involvement in cellular activities. As one of these potential mechani...
journal_title:Human molecular genetics
pub_type: 临床试验,杂志文章
doi:10.1093/hmg/ddn022
更新日期:2008-05-01 00:00:00
abstract::Slow-channel syndrome (SCS) is a congenital myasthenic disorder caused by point mutations in subunits of skeletal muscle acetylcholine receptor leading to Ca(2+) overload and degeneration of the postsynaptic membrane, nuclei and mitochondria of the neuromuscular junction (NMJ). In both SCS muscle biopsies and transgen...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddt397
更新日期:2014-01-01 00:00:00
abstract::Various small molecule pharmacologic agents with different known functions produce similar outcomes in diverse Mendelian and complex disorders, suggesting that they may induce common cellular effects. These molecules include histone deacetylase inhibitors, 4-phenylbutyrate (4PBA) and trichostatin A, and two small mole...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/dds247
更新日期:2012-10-01 00:00:00
abstract::Parkinson disease (PD) is the second most common neurodegenerative disorder. We studied 754 affected individuals, comprising 425 sibling pairs, to identify PD susceptibility genes. Screening of the parkin gene was performed in a subset of the sample having earlier age of PD onset or a positive LOD score with a marker ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddg270
更新日期:2003-10-15 00:00:00
abstract::Spinocerebellar ataxia type 1 (SCA1) is one of nine dominantly inherited neurodegenerative diseases caused by polyglutamine tract expansion. In SCA1, the expanded polyglutamine tract is in the ataxin-1 (ATXN1) protein. ATXN1 is part of an in vivo complex with retinoid acid receptor-related orphan receptor alpha (Rora)...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddr108
更新日期:2011-06-01 00:00:00
abstract::The RASopathies are a group of genetic syndromes caused by upregulated RAS signaling. Noonan syndrome (NS), the most common entity among the RASopathies, is characterized mainly by short stature, cardiac anomalies and distinctive facial features. Mutations in multiple RAS-MAPK pathway-related genes have been associate...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddz108
更新日期:2020-07-21 00:00:00
abstract::Retinitis pigmentosa (RP), a genetically heterogeneous group of retinopathies that occur in both non-syndromic and syndromic forms, is caused by mutations in ∼100 genes. Although recent advances in next-generation sequencing have aided in the discovery of novel RP genes, a number of the underlying contributing genes a...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddu291
更新日期:2014-11-01 00:00:00
abstract::IGF2 loss of imprinting (LOI) is fairly prevalent and implicated in the pathogenesis of human cancer and developmental disease; however, the causes of this phenomenon are largely unknown. We determined whether the post-weaning diet of mice affects allelic expression and CpG methylation of Igf2. C57BL/6JxCast/EiJ F1 hy...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddi484
更新日期:2006-03-01 00:00:00
abstract::Targeting of numerous transmembrane proteins to the cell surface is thought to depend on their recognition by cargo receptors that interact with the adaptor machinery for anterograde traffic at the distal end of the Golgi complex. We report here on consortin, a novel integral membrane protein that is predicted to be i...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddp490
更新日期:2010-01-15 00:00:00
abstract::Meiotic crossovers in the human genome cluster into highly localized hotspots identifiable indirectly from patterns of DNA diversity and directly by high-resolution sperm typing. Little is known about factors that control hotspot activity and the apparently rapid turnover of hotspots during recent evolution. Clues can...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddl063
更新日期:2006-05-01 00:00:00
abstract::Selective loss of dopaminergic neurons is the final common pathway in Parkinson's disease. Expression of Parkin associated endothelin-receptor like receptor (Pael-R) in mouse brain was achieved by injecting adenoviral vectors carrying a modified neuron-specific promoter and Cre recombinase into the striatum. Upregulat...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddl439
更新日期:2007-01-01 00:00:00
abstract::The transient receptor potential vanilloid 1 (TRPV1) protein is a pain receptor that elicits a hot sensation when an organism eats the capsaicin of red chili peppers. This calcium (Ca2+)-permeable cation channel is mostly expressed in the peripheral nervous system sensory neurons but also in the central nervous system...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddz276
更新日期:2020-01-15 00:00:00
abstract::Mutations in the survival motor neuron (SMN1) gene lead to the neuromuscular disease spinal muscular atrophy (SMA). Although SMA is primarily considered as a motor neuron disease, the importance of muscle defects in its pathogenesis has not been fully examined. We use both primary cell culture and two different SMA mo...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddu142
更新日期:2014-08-15 00:00:00
abstract::GM2 gangliosidoses are a group of lysosomal storage disorders which include Sandhoff disease and Tay-Sachs disease. Dysregulation of glutamate receptors has been recently postulated in the pathology of Sandhoff disease. Glutamate receptor association with neuronal pentraxins 1 and 2, and the neuronal pentraxin recepto...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddw422
更新日期:2017-02-15 00:00:00
abstract::Multiple intergenic single-nucleotide polymorphisms (SNPs) near hedgehog interacting protein (HHIP) on chromosome 4q31 have been strongly associated with pulmonary function levels and moderate-to-severe chronic obstructive pulmonary disease (COPD). However, whether the effects of variants in this region are related to...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddr569
更新日期:2012-03-15 00:00:00
abstract::Non-syndromic neurosensory autosomal recessive deafness (NSRD) is the most common form of genetic hearing loss. Previous studies defined at least 15 human NSRD loci. Recently we demonstrated that DFNB1, located on the long arm of chromosome 13, accounts for approximately 80% of cases in the Mediterranean area. Further...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/6.9.1605
更新日期:1997-09-01 00:00:00
abstract::Mutations in fibroblast growth factor receptors (FGFRs) cause human birth defect syndromes and are associated with a variety of cancers. Although forced expression of mutant activated FGFRs has been shown to oncogenically transform some immortal cell types, their activity in primary cells remains unclear. Here, we sho...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddp195
更新日期:2009-07-15 00:00:00
abstract::Development of gene therapy for the muscular dystrophies represents a daunting challenge requiring significant advances in our knowledge of the defective genes, muscle promoters, viral vectors, immune system surveillance and methods for systemic delivery of vectors. However, tremendous progress has been made in develo...
journal_title:Human molecular genetics
pub_type: 杂志文章,评审
doi:10.1093/hmg/11.20.2355
更新日期:2002-10-01 00:00:00
abstract::Cerebrospinal fluid amyloid-beta 1-42 (Aβ1-42) and phosphorylated Tau at position 181 (pTau181) are biomarkers of Alzheimer's disease (AD). We performed an analysis and meta-analysis of genome-wide association study data on Aβ1-42 and pTau181 in AD dementia patients followed by independent replication. An association ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddu372
更新日期:2014-12-15 00:00:00
abstract::Changes to islet cell identity in response to type 2 diabetes (T2D) have been reported in rodent models, but are less well characterized in humans. We assessed the effects of aspects of the diabetic microenvironment on hormone staining, total gene expression, splicing regulation and the alternative splicing patterns o...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddz094
更新日期:2019-08-15 00:00:00
abstract::Type V collagen is a constituent of type I collagen-rich fibrils in many connective tissues and is a regulator of fibril diameter. In tissues, type V collagen is a heterotrimer with the molecular structure: alpha 1(V)2 alpha 2(V) or alpha 1(V) alpha 2(V) alpha 3(V). We report that genomic polymorphisms at the pro alph...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/5.11.1733
更新日期:1996-11-01 00:00:00
abstract::Alzheimer's disease (AD) is characterized by both amyloid and Tau pathologies. The amyloid component and altered cholesterol metabolism are closely linked, but the relationship between Tau pathology and cholesterol is currently unclear. Brain cholesterol is synthesized in situ and cannot cross the blood-brain barrier:...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddv268
更新日期:2015-11-01 00:00:00