![]() USH2A mutation and specific driver mutation subtypes are associated with clinical efficacy of immune checkpoint inhibitors in lung cancer.Whole genome sequencing for USH2A-associated disease reveals several pathogenic deep-intronic variants that are amenable to splice correction.Characterizing the genotypic spectrum of retinitis pigmentosa in East Asian populations: a systematic review.Natural Disease Course in Usher Syndrome Patients Harboring USH2A Variant p.Cys870* in Exon 13, Amenable to Exon Skipping Therapy.USH2A mutational spectrum causing syndromic and non-syndromic retinal dystrophies in a large cohort of Mexican patients.Expression Biased expression in liver (RPKM 1.7), testis (RPKM 0.3) and 1 other tissue See more Orthologs mouse all NEW Try the new Gene table Multiple transcript variants encoding different isoforms have been found for this gene. Mutations within this gene have been associated with Usher syndrome type IIa and retinitis pigmentosa. The protein is found in the basement membrane, and may be important in development and homeostasis of the inner ear and retina. Full characterization of this model will lead to a better understanding of the human disease and will be a valuable resource to develop targeted therapies for treatment.Full Name usherin provided by HGNC Primary source HGNC:HGNC:12601 See related Ensembl:ENSG00000042781 MIM:608400 AllianceGenome:HGNC:12601 Gene type protein coding RefSeq status REVIEWED Organism Homo sapiens Lineage Eukaryota Metazoa Chordata Craniata Vertebrata Euteleostomi Mammalia Eutheria Euarchontoglires Primates Haplorrhini Catarrhini Hominidae Homo Also known as US2 RP39 USH2 dJ1111A8.1 Summary This gene encodes a protein that contains laminin EGF motifs, a pentaxin domain, and many fibronectin type III motifs. Data are consistent with USH patients having a later onset visual impairment compared to hearing loss. GFP expression evaluations allow for further study of possible systemic effects usherin may have in conjunction with deafness/blindness. This mouse is the first USH2A model with a human mutation it is also the first USH model to show retinal dysfunction without rearing in higher cyclic light. Furthermore, KI mice at P360 have a significant decline in scotopic and photopic amplitudes. Retinal evaluations via IHC and ERG up to P180 appear normal however there is a delay in transducin and arrestin translocation upon light exposure as early as P30. SEM evaluation of the cochlea showed outer hair cell abnormalities consistent with hearing loss at postnatal day 180 (P180). GFP expression identified new tissues expressing usherin that have not been previously reported and will be explored further for structural and functional abnormalities. The KI mutation is present in the endogenous locus, truncated message is stable, and the mutant protein is expressed in photoreceptors and hair cells. Electroretinography (ERG) was used to assess retinal function. ![]() Scanning electron microscopy (SEM) and immunohistochemistry (IHC) were used to evaluate retinal and cochlear structure. RT-PCR and immunoblotting were used to assess message and protein levels. In addition to introducing the c.2299delG mutation, the KI construct contains an internal ribosomal entry site followed by GFP (to assess promoter activity). The c.2299delG mutation causes a frame shift and premature stop codon. To study the role of usherin in audiovisual impairment we have generated and characterized a knockin (KI) mouse model expressing the human c.2299delG mutation. The c.2299delG mutation in usherin is the most common cause for USH type 2A in patients. Usher syndrome (USH) is the leading cause of combined deafness and blindness but the mechanisms of sensory loss are unknown.
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