Forward genetic screening using fundus spot scale identifies an essential role for Lipe in murine retinal homeostasis.

ABSTRACT: Microglia play a role in the pathogenesis of many retinal diseases. Fundus spots in mice often correlate with the accumulation of activated subretinal microglia. Here we use a semiquantitative fundus spot scoring scale in combination with an unbiased, state-of-the-science forward genetics pipeline to identify causative associations between chemically induced mutations and fundus spot phenotypes. Among several associations, we focus on a missense mutation in Lipe linked to an increase in yellow fundus spots in C57BL/6J mice. Lipe^-/- mice generated using CRISPR-Cas9 technology are found to develop accumulation of subretinal microglia, a retinal degeneration with decreased visual function, and an abnormal retinal lipid profile. We establish an indispensable role of Lipe in retinal/

SUBMITTER: Yuksel S 

PROVIDER: S-EPMC10192353 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature