PROGRESSION OF COCHLEAR AND RETINAL DEGENERATION IN THE TUBBY (RD5) MOUSE

Mice homozygous for a defect of the tub (rd5) gene exhibit cochlear an d retinal degeneration combined with obesity, and resemble certain hum an autosomal recessive sensory deficit syndromes. To establish the pro gressive nature of sensory cell loss associated with the tub gene, and to differentiate tub-related losses from those associated with the C5 7 background on which tub arose, we evaluated cochleas and retinas fro m tub/tub, tub/+, and +/+ mice, aged 2 weeks to 1 year by light and el ectron microscopy. Cochleas from mice of all three genotypes show prog ressive inner (IHC) and outer hair cell (OHC) loss. Relative to tub/and +/+ animals, however, tub homozygotes show accelerated OHC loss, a ffecting the extreme cochlear base (hook region) by 1 month, and the a pex by 6 months. IHC loss in tub/tub animals is accelerated in the bas al half of the cochlea, affecting the hook region by 6 months. Spiral ganglion cell losses were observed only in tub/tub mice, and only in t he cochlear base. Retinas of tub/tub mice are abnormal at maturity, ex hibiting shortened photoreceptor outer segments by 2 weeks, and progre ssive photoreceptor loss thereafter. Because the tub mutation causes d egeneration of sensory cells in the ear and eye but has no other neuro logical effects, tubby mice hold unique promise for the study of human syndromic sensory loss.