| http://purl.uniprot.org/citations/28356706 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/28356706 | http://www.w3.org/2000/01/rdf-schema#comment | "PurposeFamilial exudative vitreoretinopathy (FEVR) is caused by mutations in the genes encoding low-density lipoprotein receptor-related protein (LRP5) or its interacting partners, namely frizzled class receptor 4 (FZD4) and norrin cystine knot growth factor (NDP). Mouse models for Lrp5, Fzd4, and Ndp have proven to be important for understanding the retinal pathophysiology underlying FEVR and systemic abnormalities related to defective Wnt signaling. Here, we report a new mouse mutant, tvrm111B, which was identified by electroretinogram (ERG) screening of mice generated in the Jackson Laboratory Translational Vision Research Models (TVRM) mutagenesis program.MethodsERGs were used to examine outer retinal physiology. The retinal vasculature was examined by in vivo retinal imaging, as well as by histology and immunohistochemistry. The tvrm111B locus was identified by genetic mapping of mice generated in a cross to DBA/2J, and subsequent sequencing analysis. Gene expression was examined by real-time PCR of retinal RNA. Bone mineral density (BMD) was examined by peripheral dual-energy X-ray absorptiometry.ResultsThe tvrm111B allele is inherited as an autosomal recessive trait. Genetic mapping of the decreased ERG b-wave phenotype of tvrm111B mice localized the mutation to a region on chromosome 19 that included Lrp5. Sequencing of Lrp5 identified the insertion of a cytosine (c.4724_4725insC), which is predicted to cause a frameshift that disrupts the last three of five conserved PPPSPxS motifs in the cytoplasmic domain of LRP5, culminating in a premature termination. In addition to a reduced ERG b-wave, Lrp5tvrm111B homozygotes have low BMD and abnormal features of the retinal vasculature that have been reported previously in Lrp5 mutant mice, including persistent hyaloid vessels, leakage on fluorescein angiography, and an absence of the deep retinal capillary bed.ConclusionsThe phenotype of the Lrp5tvrm111B mutant includes abnormalities of the retinal vasculature and of BMD. This model may be a useful resource to further our understanding of the biological role of LRP5 and to evaluate experimental therapies for FEVR or other conditions associated with LRP5 dysfunction."xsd:string |
| http://purl.uniprot.org/citations/28356706 | http://purl.uniprot.org/core/author | "Rao S."xsd:string |
| http://purl.uniprot.org/citations/28356706 | http://purl.uniprot.org/core/author | "Nishina P.M."xsd:string |
| http://purl.uniprot.org/citations/28356706 | http://purl.uniprot.org/core/author | "Peachey N.S."xsd:string |
| http://purl.uniprot.org/citations/28356706 | http://purl.uniprot.org/core/author | "Anand-Apte B."xsd:string |
| http://purl.uniprot.org/citations/28356706 | http://purl.uniprot.org/core/author | "Charette J.R."xsd:string |
| http://purl.uniprot.org/citations/28356706 | http://purl.uniprot.org/core/author | "Ackert-Bicknell C.L."xsd:string |
| http://purl.uniprot.org/citations/28356706 | http://purl.uniprot.org/core/author | "Godfrey D.A."xsd:string |
| http://purl.uniprot.org/citations/28356706 | http://purl.uniprot.org/core/author | "Earp S.E."xsd:string |
| http://purl.uniprot.org/citations/28356706 | http://purl.uniprot.org/core/author | "Bell B.A."xsd:string |
| http://purl.uniprot.org/citations/28356706 | http://purl.uniprot.org/core/date | "2017"xsd:gYear |
| http://purl.uniprot.org/citations/28356706 | http://purl.uniprot.org/core/name | "Mol Vis"xsd:string |
| http://purl.uniprot.org/citations/28356706 | http://purl.uniprot.org/core/pages | "140-148"xsd:string |
| http://purl.uniprot.org/citations/28356706 | http://purl.uniprot.org/core/title | "A mutagenesis-derived Lrp5 mouse mutant with abnormal retinal vasculature and low bone mineral density."xsd:string |
| http://purl.uniprot.org/citations/28356706 | http://purl.uniprot.org/core/volume | "23"xsd:string |
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