KITADA Kazuhiro HOKKAIDO UNIVERSITY, CENTER FOR ADVANCED SCIENCE AND TECHNOLOGY, ASSOCIATE PROFESSOR, 先端科学技術共同センター, 助教授 (70263093)
MORI Masayuki SHINSYU UNIVERSITY, GRADUATE SCHOOL OF MEDICINE, ASSOCIATE PROFESSOR, 医学部, 助教授 (60273190)
KURAMOTO Takashi KYOTO UNIVERSITY, GRADUATE SCHOOL OF MEDICINCE, ASSISTANT PROFESSOR, 医学研究科, 講師 (20311409)
KUWAMURA Mitsuru OSAKA PREFECTURE UNIVERSITY, GRADUATE SHOOL OF AGRICULTURE AND BIOLOGICAL SCIENCE, ASSISTANT PROFESSOR, 農学生命科学研究科, 助手 (20244668)
YOKOI Norihide KOBE UNIVERSITY, GRADUATE SCHOOL OF MEDICINE, ASSOCIATE PROFESSOR, 医学系研究科, 客員助教授 (70311610)
Considering the rapid progress of the rat genome sequencing project in the US, we have put our efforts into the identification of causative genes in neurological mutant rats. For that reason, we constructed several fine comparative maps in genomic regions where the causative genes of the mutants are located. Twelve neurological mutant rat strains we studied in this project were as follows. Tremor rats, Zitter rats, mv rats, KZC rats, cvd rats, hob rats, SCR rats, qc rats, dmy rats, dfk rats, vf rats, and furue rats. By positional cloning for tremor rats, a genomic deletion was found within the critical region in which the aspartoacylase gene is located. We found a marked decrease in Attractin mRNA in the brain of the zi/zi rat and identified zi as an 8-bp deletion at a splice donor site of Atrn. A genomic deletion including exon 1 of the mv rats was detected by genomic and sequence analyses. As for the KDP rats, we identified a nucleotide insertion mutation, probably null allele, in the reelin gene. Rat neurological mutations cvd and hob were caused by mutations in the netrin-1 receptor gene Unc5h3. Abnormal vacuolation in the CNS of the vf rats was found to be controlled by a recessive gene on Chr8. As for the cataract phenotype in the SCR rats, a mutation of oxidosqualene cyclase gene that is located in the critical mapping region was found. Positional candidate genes for dmy and dfk rats were found and analyzed in detail. To clone the causative gene Cblb of Iddm/kdp 1 in KDP rats, a precise genetic and comparative map of rat Chr11 and mouse Chr16 in the vicinity of the locus was first constructed. Toward the identification of the dmy mutation, we determined the corresponding genomic region on mouse Chr13 and constructed its fine genetic and physical maps.