Genetic background determines severity of Loxl1-mediated systemic and ocular elastosis in mice.

Pseudoexfoliation syndrome (PEX) is a systemic, age-related disorder characterized by elastosis and extracellular matrix deposits. Its most significant ocular manifestation is an aggressive form of glaucoma associated with variants in the gene coding for lysyl oxidase-like 1 (LOXL1). Depending upon the population, variants in LOXL1 can impart risk or protection for PEX, suggesting the importance of genetic context. Since LOXL1 protein levels are lower and elastosis higher in people with PEX, we studied Loxl1 deficient mice on three different genetic backgrounds, C57BL/6 (BL/6), 129S.C57BL/6 (50/50) and 129S. Early onset and high prevalence of spontaneous pelvic organ prolapse (POP) in BL/6 background mice necessitated the study of mice <2 months old. Like POP, most elastosis endpoints were most severe in BL/6 mice, including skin laxity, pulmonary tropoelastin accumulation, expanded Schlemm's canal and dilated intrascleral veins. Interestingly, intraocular pressure was elevated in 50/50, depressed in BL/6 and unchanged in 129S mice. Overall, the 129S background was protective against most elastosis phenotypes studied. Thus, repair of elastin-containing tissues is impacted by abundance of LOXL1 and genetic context in young animals.