| Description |
Mouse models are extremely useful in studying human deafness syndrome, which is the most common human sensory defect. To identify novel mouse genes that are involved in inner ear development, we sought to use an induction gene trap strategy to enrich for trapping events that lead to inner ear expression. Three ES cell lines identified through the study were subjected to detailed analysis. From cell line 6-12, a novel mouse gene designated prtb was identified which encodes a proline-rich protein with high homology with its human homolog. prtb expression was transient in the heart of E 11.5 and E 12.5 mouse embryos and very strong in various regions of the adult brain. However, although the gene trap insertion generated a null allele for prtb, mice homozygous for prtb[gt] mutation did not display any detectable abnormalities. This was likely due to functional redundancy. From cell line 24-B9, punc, a mouse gene that belongs to the neural Ig superfamily was identified. To understand its function, we disrupt punc expression by gene targeting and generate Punc deficient mouse. During embryogenesis, punc was expressed strongly in the limb buds as well as the central nervous system, including the spinal cord and the brain. In adult, its expression was detected in the cochlear of the inner ear and various regions of the brain, most notably, the cerebellum and the hippocampus. Mice homozygous for punc mutation performed poorly on the rotorod test, suggesting for a function of Punc in cerebellum control of motor coordination. In 33-B12 ES cells, the gene trap vector integrated into an intron of the mouse Ap3b1 gene, which encodes the beta-3A subunit of the AP-3 complex. To obtain genetic evidence that Ap3b1 is the candidate gene for a preexisting mouse coat color mutant pearl, we disrupted the Ap3b1 gene via homologous recombination and generated a null allele Ap3b1[LN]. Mice homozygous for the mutation displayed diluted coat color like pearl mice. In addition, in the absence of the beta-3A subunit, other subunits of the AP-3 complex destabilize. As a consequence, LampI, LampII and Tyrosinase all mislocalize in the cells. These results demonstrated that the AP-3 complex is involved in transporting certain cargo proteins to the lysosome/melanosome |
