| Budget Amount *help |
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 2004: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2003: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Research Abstract |
Inherited syndromic sensorineural deafness has been reported in several inbreed dogs. Congenital deafness is frequently associated with pigmentation disorders such as white coat color and blue eyes. These findings are similar to those of Waardenburg syndrome in human. We interpreted the dog sydromic deafness with pigmentation disorder as the counterpart of Waardenburg syndrome and analyzed the genes associated with Waardenburg syndrome including MITF, PAX3 and SOX10 genes in affected dogs. Although several isoforms were reported in human, only two isoforms for MITF gene have been described in dogs. Cloning of canine MITF cDNA in this study presented that, in addition to two isoforms of MITF-M and MITF-H, MITF-A isoform was expressed in dog tissues. Analysis of the expression of MITF isoforms showed that isoforms MITF-H and MITF-A expressed ubiquitous, but MITF-M expression was observed in specific organs including kidney, cerebrum, cerebellum, heart and upper digestive system in normal dog by RT-PCR methods. Although the coding regions of three isoforms for canine MITF gene was amplified and sequenced, no mutation was detected in the affected dogs with congenital syndromic deafness. PAX3 and SOX10 genes are also associated with congenital syndromic hearing disorder. For determination of gene construction, cDNA fragments were cloned and analyzed from a healthy dog sample. After the determination of each gene structure, each exon coding amino acids was amplified by primers constructed in introns and sequenced. However, No differences of nucleotide that induced the changes of amino acid was detected between the affected dogs and normal healthy dog. In this study, although the mutations were not detected in three genes associated with Waarenburg syndrome, this method will be able to analysis on congenital deafness in dogs.
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