Mouse microphthalmia transcription factor (Mitf) mutations affect the 
development of four cell types: melanocytes, mast cells, osteoclasts, and 
pigmented epithelial cells of the eye. The mutations are phenotypically diverse 
and can be arranged in an allelic series. In humans, MITF mutations cause 
Waardenburg syndrome type 2A (WS2A) and Tietz syndrome, autosomal dominant 
disorders resulting in deafness and hypopigmentation. Mitf mice thus represent 
an important model system for the study of human disease. Here we report the 
complete exon/intron structure of the mouse Mitf gene and show it to be similar 
to the human gene. We also found that the mouse gene is transcriptionally 
complex and is capable of generating at least 13 different Mitf isoforms. Some 
of these isoforms are missing important functional domains of the protein, 
suggesting that they might play an inhibitory role in Mitf function and signal 
transduction. In addition, we determined the molecular basis for six 
microphthalmia mutations. Two of the mutations are reported for the first time 
here (Mitf(mi-enu198) and Mitf(mi-x39)), while the others (Mitf(mi-ws), 
Mitf(mi-bws), Mitf(mi-ew), and Mitf(mi-di)) have been described but the 
molecular basis for the mutation not determined. When analyzed in terms of the 
genomic and transcriptional data presented here, it is apparent that these 
mutations result from RNA processing or transcriptional defects. Interestingly, 
three of the mutations (Mitf(mi-x39), Mitf(mi-bws), and Mitf(mi-ws)) produce 
proteins that are missing important functional domains of the protein identified 
in in vitro studies, further confirming a biological role for these domains in 
the whole animal.