Characterization of Ws Mutant Allele of Rats: A 12-Base Deletion in Tyrosine Kinase Domain of c-kit Gene

• Published in: Blood Vol. 78; no. 8; pp. 1942 - 1946
• Main Authors: Tsujimura, Tohru, Hirota, Seiichi, Nomura, Shintaro, Niwa, Yoshiki, Yamazaki, Masaru, Tono, Toshiharu, Morii, Eiichi, Kim, Hyung-Min, Kondo, Kyoji, Nishimune, Yoshitake, Kitamura, Yukihiko
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 15.10.1991; The Americain Society of Hematology
• Subjects: Alleles; Animals; Base Sequence; Biological and medical sciences; Chromosome Deletion; Fundamental and applied biological sciences. Psychology; Genetics of eukaryotes. Biological and molecular evolution; Molecular Sequence Data; Protein-Tyrosine Kinases - genetics; Rats; Rats, Inbred BN; Rats, Mutant Strains - genetics; Tyrosine; Mutation; Gene; Animal; Result
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V78.8.1942.1942

Homozygous mutant rats at the newly found white spotting (Ws) locus were anemic and deficient in mast cells and melanocytes. Because the phenotype of Ws/ Ws rats resembled the phenotype of mice possessing a double-gene dose of mutant alleles at the W locus and because the c-kit gene was mapped at the W locus of mice, we characterized the c-kit gene of Ws/Ws rats. The authentic sequence of the rat c-kit cDNA was determined by using a cDNA library prepared from the hippocampus of Sprague-Dawley rats. The c-kit cDNA of Ws/Ws and normal (+/+) control rats was obtained by reverse transcriptase modification of the polymerase chain reaction. When compared with the authentic sequence, a deletion of 12 bases was found in the c-kit cDNA of Ws/Ws rats. This change was shown to be a result of the deletion of the genomic DNA. Four amino acids encoded by the deleted 12 bases (ie, Val-Lys-Gly-Asn) were located at two amino acids downstream from the tyrosine autophosphorylation site in the c-kit kinase and were conserved not only in mouse and human c-kit kinases but also in mouse and human c-fms kinases (ie, receptors of colony-stimulating factor-1). Taken together, the Ws/Ws rat is the first characterized mutant of the c-kit gene in an animal species other than the mouse.© 1991 by The American Society of Hematology. 0006-4971/91 / 7808-0007$3.00/0