Using BXD mouse strains in vision research: A systems genetics approach

• Type of Material: Article
• Authors: Eldon Geisert Jr, Emory University; Robert W. Williams, University of Tennessee
• Language: English
• Date: 2020-03-06
• Publisher: MOLECULAR VISION
• Publication Version: Final Published Version
• Copyright Statement: © 2020 Molecular Vision.
• License: Creative Commons Attribution 4.0 International
• Title of Journal or Parent Work: MOLECULAR VISION
• Volume: 26
• Start Page: 173
• End Page: 187
• Grant/Funding Information: This study was supported by an Unrestricted Grant from Research to Prevent Blindness, NEI grant R01EY017841 (E.E.G.), Owens Family Glaucoma Research Fund, P30EY06360 (Emory Vision Core) and DoD CDMRP Grant W81XWH-12-1-0255 from the USA Army Medical Research & Materiel Command and the Telemedicine and Advanced Technology (E.E.G.). GeneNetwork supported by NIGMS (R01GM123489), NIDA (P30DA044223) and the UT Center for Integrative and Translational Genomics, and funds from the UT-ORNL Governor’s Chair (R.W.W.).
• Keywords: GENOME-WIDE ASSOCIATION; Science & Technology; Ophthalmology; COLLABORATIVE CROSS; Biochemistry & Molecular Biology; RETINAL GANGLION; INTRAOCULAR-PRESSURE; WALLERIAN DEGENERATION; TRABECULAR MESHWORK; OPEN-ANGLE GLAUCOMA; CENTRAL CORNEAL THICKNESS; OCULAR HYPERTENSION; CELL NUMBER; Life Sciences & Biomedicine
• Research Categories: Chemistry, Biochemistry; Biology, Cell; Health Sciences, Opthamology; Biology, Genetics

Abstract

We illustrate the growing power of the BXD family of mice (recombinant inbred strains from a cross of C57BL/6J and DBA/2J mice) and companion bioinformatic tools to study complex genome-phenome relations related to glaucoma. Over the past 16 years, our group has integrated powerful murine resources and web-accessible tools to identify networks modulating visual system traits—from photoreceptors to the visual cortex. Recent studies focused on retinal ganglion cells and glaucoma risk factors, including intraocular pressure (IOP), central corneal thickness (CCT), and susceptibility of cellular stress. The BXD family was exploited to define key gene variants and then establish linkage to glaucoma in human cohorts. The power of this experimental approach to precision medicine is highlighted by recent studies that defined cadherin 11 (Cdh11) and a calcium channel (Cacna2d1) as genes modulating IOP, Pou6f2 as a genetic link between CCT and retinal ganglion cell (RGC) death, and Aldh7a1 as a gene that modulates the susceptibility of RGCs to death after elevated IOP. The role of three of these gene variants in glaucoma is discussed, along with the pathways activated in the disease process.