Mice Homozygous for a Deletion in the Glaucoma Susceptibility Locus INK4 Show Increased Vulnerability of Retinal Ganglion Cells to Elevated Intraocular Pressure

The American Journal of Pathology
Shan Gao, Tatjana C Jakobs

Abstract

A genomic region located on chromosome 9p21 is associated with primary open-angle glaucoma and normal tension glaucoma in genome-wide association studies. The genomic region contains the gene for a long noncoding RNA called CDKN2B-AS, two genes that code for cyclin-dependent kinase inhibitors 2A and 2B (CDKN2A/p16(INK4A) and CDKN2B/p15(INK4B)) and an additional protein (p14(ARF)). We used a transgenic mouse model in which 70 kb of murine chromosome 4, syntenic to human chromosome 9p21, are deleted to study whether this deletion leads to a discernible phenotype in ocular structures implicated in glaucoma. Homozygous mice of this strain were previously reported to show persistent hyperplastic primary vitreous. Fundus photography and optical coherence tomography confirmed that finding but showed no abnormalities for heterozygous mice. Optokinetic response, eletroretinogram, and histology indicated that the heterozygous and mutant retinas were normal functionally and morphologically, whereas glial cells were activated in the retina and optic nerve head of mutant eyes. In quantitative PCR, CDKN2B expression was reduced by approximately 50% in the heterozygous mice and by 90% in the homozygous mice, which suggested that the CDKN2B kn...Continue Reading

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Citations

Dec 23, 2016·Journal of Medical Genetics·Peixing WanYehong Zhuo
Apr 19, 2017·The Journal of Experimental Medicine·Daniel SunTatjana C Jakobs
Jun 18, 2017·Frontiers in Neuroscience·Franklin D EchevarriaRebecca M Sappington
Jun 22, 2019·Annual Review of Vision Science·Ileana SotoGareth R Howell
Oct 30, 2019·Investigative Ophthalmology & Visual Science·Hiroshi TawarayamaToru Nakazawa
Aug 17, 2020·Investigative Ophthalmology & Visual Science·Hang-Jing WuRachel W Kuchtey

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