Abstract
NOD/ShiLtJ (previously NOD/LtJ) inbred mice show polygenic autoimmune disease and are commonly used to model autoimmune-related type I diabetes, as well as Sjogren's syndrome. They also show rapidly progressing hearing loss, partly due to the combined effects of Cdh23ahl and Ahl2. Congenic NOD.NON-H2nb1/LtJ mice, which carry corrective alleles within the H2 histocompatibility gene complex, are free from diabetes and other overt signs of autoimmune disease, but still exhibit rapidly progressive hearing loss. Here we show that cochlear pathology in these congenics broadly includes hair cell and neuronal loss, plus endocochlear potential (EP) decline from initially normal values after two months of age. The EP reduction follows often dramatic degeneration of capillaries in stria vascularis, with resulting strial degeneration. The cochlear modiolus also features perivascular inclusions that resemble those in some mouse autoimmune models. We posit that cochlear hair cell/neural and strial pathology arise independently. While sensory cell loss may be closely tied to Cdh23ahl and Ahl2, the strial microvascular pathology and modiolar anomalies we observe may arise from alleles on the NOD background related to immune function. Age-associated EP decline in NOD.NON-H2nb1 mice may model forms of strial age-related hearing loss caused principally by microvascular disease. The remarkable strial capillary loss in these mice may also be useful for studying the relation between strial vascular insufficiency and strial function.