1998 Fiscal Year Final Research Report Summary
A novel type of myosin encoded by the mouse deafness gene shaker-2
| Project/Area Number |
09470029
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General medical chemistry
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| Research Institution | NIIGATA UNIVERSITY |
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Principal Investigator |
KOMINAMI Ryo Niigata University School of Medicine Associate Professor, 医学部, 教授 (40133615)
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| Co-Investigator(Kenkyū-buntansha) |
TAKAHASHI Yoshiaki Niigata University School of Medicine Lecturer, 医学部, 講師 (60115045)
MISHIMA Yukio Niigata University School of Medicine Professor, 医学部, 助教授 (30166003)
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| Project Period (FY) |
1997 – 1998
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| Keywords | GENETIC DEAFNESS / POSITIONAL CLONING / GENOME ANALYSIS / MYOSIN GENE |
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| Research Abstract |
Genetic hearing impairment affects about one in 2,000 children at birth. The majority of genetic deafness is non-syndromic, in which hearing loss is not associated with any other abnormalities. Autosomal recessive forms of non-syndromic deafness (DFNB) account for most profound deafness and are almost exclusively due to abnormalities of the sensory neuroepithelia of the inner ear. Ten loci for such deafness have been mapped and mutations in two genes encoding unconventional myosin VIIA and connexin 26 have been identified. One locus, DFNB3, is assigned to 17p11.2-17q12 which is homologous to the shaker-2 (sh-2) locus on mouse chromosome 11. Homozygous sh-2 mice exhibit the circling, headtossing, deafness, and hyperactivity seen in mice with inner ear defects and some of these symptoms resemble those of DFNB3, implying that the same unidentified gene underlies DFNB3 and sh-2.
We constructed a contig consisting of 21 BAC clones across an approximately 700-kb region which covers the entire nonrecombinant region of sh-2. With this genetic and physical maps, we carried out a positional cloning approach to identify the sh-2 mutation. Here we report the use of a positional cloning approach to show that the gene mutated in sh-2 mice encodes a novel type of unconventional myosin. A G-to-A transition changing cysteine to tyrosine in the conserved actin binding domain is detected in sh-2 but absent in laboratory strains and wild mice belonging to different mouse subspecies and species. Based on conserved synteny and the mutation, the novel myosin gene is a strong candidate for DFNB3.
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Research Products
(4 results)
