Retina-specific loss of Ikbkap/Elp1 causes mitochondrial dysfunction that leads to selective retinal ganglion cell degeneration in a mouse model of familial dysautonomia.

ABSTRACT: Familial dysautonomia (FD) is an autosomal recessive disorder marked by developmental and progressive neuropathies. It is caused by an intronic point-mutation in the IKBKAP/ELP1 gene, which encodes the inhibitor of κB kinase complex-associated protein (IKAP, also called ELP1), a component of the elongator complex. Owing to variation in tissue-specific splicing, the mutation primarily affects the nervous system. One of the most debilitating hallmarks of FD that affects patients' quality of life is progressive blindness. To determine the pathophysiological mechanisms that are triggered by the absence of IKAP in the retina, we generated retina-specific Ikbkap conditional knockout (CKO) mice using Pax6-Cre, which abolished Ikbkap expression in all cell types of the retina. Although sensory and

SUBMITTER: Ueki Y 

PROVIDER: S-EPMC6078410 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature