THE MURINE TUB (RD5) MUTATION IS NOT ASSOCIATED WITH A PRIMARY AXONEMAL DEFECT

Some genetic syndromes causing loss of hearing, and vision, such as so me forms of Usher's syndrome, also cause reduced sperm cell motility, bronchiectasis, and other pathologies involving cilia- and flagella-be aring cells. In some Usher's patients, ultrastructural defects of axon emes within photoreceptor ciliary bridges, nasal cilia, and sperm cell flagella have been found, indicating a primary defect of axonemal con formation. Mice homozygous for the tub (rd15) mutation exhibit progres sive retinal degeneration, sensorineural hearing loss, reduced fertili ty, and obesity, and presently represent the only animal model with ne uroepithelial degeneration of both cochlea and retina without other ne urological abnormalities. They provide a good phenotypic match to huma n genetic sensory syndromes, particularly human sensory/obesity syndro mes, such as Alstrom's and Bardet/Biedl, although no human candidate g enes have been identified. Because of their unique phenotype, tubby mi ce are an appropriate model in which to look for a primary axonemal de fect. We studied the axonemal ultrastructure of photoreceptors and spe rm cells and performed functional testing of sperm in tub/tub mice bef ore and after the onset of obesity. Approximately 15% of photoreceptor axonemes appeared abnormal in tub/tub animals, compared to 0% in cont rols. Both tub homozygotes and controls exhibited approximately 10% ab normal sperm cell axonemes, and no differences in sperm cell motile fu nction were found at any age. The modest occurrence of axonemal defect s in photoreceptors of tub/tub animals is likely to be a secondary eff ect of retinal degeneration. We conclude that the tubby phenotype is n ot associated with a generalized defect of cilia-and flagella-bearing cells and that the tub mutation does not primarily affect axonemal str ucture.