title: Identification of the mutation in murine histidinemia (his) and genetic mapping of the murine histidase locus (Hal) on chromosome 10.
abstract: 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 approximately 4 cM distal to the insulin-like growth factor-1 locus and approximately 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.
authors: Department of Molecular and Medical Genetics, University of Toronto, Ontario, Canada.
authors: R G
authors: RG
authors: Taylor
authors: D
authors: D
authors: Grieco
authors: G A
authors: GA
authors: Clarke
authors: R R
authors: RR
authors: McInnes
authors: B A
authors: BA
authors: Taylor
mesh_terms: D000592:Amino Acid Metabolism, Inborn Errors / Q000235:genetics* / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics; D004252:DNA Mutational Analysis; D005819:Genetic Markers; D006639:Histidine / Q000097:blood*; D006638:Histidine Ammonia-Lyase / Q000235:genetics*; D008099:Liver / Q000378:metabolism; D051379:Mice / Q000235:genetics*; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000235:genetics
chemical_list: D005819:Genetic Markers; D012333:RNA, Messenger; D006639:Histidine; D004247:DNA; D006638:Histidine Ammonia-Lyase