Identification of the Mutation in Murine Histidinemia (his) and Genetic Mapping of the Murine Histidase Locus (Hal) on Chromosome 10

• Published in: Genomics (San Diego, Calif.) Vol. 16; no. 1; pp. 231 - 240
• Main Authors: Taylor, Robin G., Grieco, Donald, Clarke, Geoffrey A., McInnes, Roderick R., Taylor, Benjamin A.
• Format: Journal Article
• Language: English
• Published: San Diego, CA Elsevier Inc 01.04.1993; Elsevier
• Subjects: Amino Acid Metabolism, Inborn Errors - genetics; Amino Acid Metabolism, Inborn Errors - metabolism; Amino Acid Sequence; Animals; Base Sequence; Biological and medical sciences; Chromosome Mapping; Classical genetics, quantitative genetics, hybrids; Cloning, Molecular; DNA - genetics; DNA Mutational Analysis; Fundamental and applied biological sciences. Psychology; Genetic Markers; Genetics of eukaryotes. Biological and molecular evolution; Histidine - blood; Histidine Ammonia-Lyase - genetics; Liver - metabolism; Mice - genetics; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Mutant Strains; Molecular Sequence Data; RNA, Messenger - genetics; Vertebrata; Genetic mapping; Linkage; Nucleotide sequence; Enzyme; Rodentia; Gene expression; Vertebrata; Mammalia; Enzymatic activity; Complementary DNA; Mouse; Chromosome 10; Histidine ammonia-lyase; Histidinemia
• ISSN: 0888-7543; 1089-8646
• DOI: 10.1006/geno.1993.1164

We cloned a mouse histidase cDNA to identify the mutation in histidinemic mice (his/his) and to determine the relationship of the histidase locus (Hal) both to Chromosome 10 markers and to Hsd, the histidase activity variant locus. The his mutation, a G to A transition at nucleotide +965, changes Arg-322 to Gln (R322Q). Expression of the R322Q allele in COS cells resulted in proportionately reduced amounts of histidase protein and activity compared to the wildtype allele. Hal maps ∼4 cM distal to the insulin-like growth factor-1 locus and ∼10 cM proximal to steel. Hsd was found to be tightly linked to Hal, and the low-histidase-activity Hsd allele was associated with reduced histidase mRNA. These studies indicate that the R322Q allele reduces the stability of histidase, position Hal on the Chromosome 10 linkage map, and provide further evidence that Hsd is allelic to Hal.