| First Author | Katoh H | Year | 1991 |
| Journal | Mouse Genome | Volume | 89 |
| Pages | 572 | Mgi Jnum | J:14313 |
| Mgi Id | MGI:62484 | Citation | Katoh H, et al. (1991) Hereditary hypertyrosinemia mouse. Mouse Genome 89:572 |
| abstractText | Full text of Mouse Genome contribution: HEREDITARY HYPERTYROSINEMIA MOUSE. H. Katoh (1), F. Endo (2), K. Suzuki (3) and I. Matsuda (2). (l) Dept. of Genetics, Central Institute for Experimental Animals, Kawasaki 213, Japan, (2) Dept. of Pediatrics, Kumamoto University Medical School, Kumamoto 860, Japan, and (3) Div. of Inborn-Errors of Metabolism, Tokyo Health Service Association, Tokyo 162, Japan. INTRODUCTION Hypertyrosinemia in humans, a congenital amino acid metabolic disorder, is currently known to be of three types, each of which is caused by an abnormality in a different metabolic enzyme. We have been screening the blood levels of amino acids in 24 strains of mice including 19 inbred strains newly obtained from the ICR outbred strain. As a result, one strain with hypertyrosinemia was found. In this study, we performed enzymological and genetic studies on this disorder. MATERIALS and METHODS The blood levels of amino acids were measured using whole blood or plasma. Tyrosine metabolic enzymes were measured using liver as the materials. RESULTS and DISCUSSION Amino acid screening showed that the III strain is hypertyrosinemic (about 20mg/dl at 1mo of age) and the others are low (<3mg/dl). This strain does not show any clinical symptoms by appearance, and reproductive activity and life span of the strain are normal. Three tyrosine metabolic enzymes were measured in the III strain and the IST strain as control. Activities of fumarylacetoacetase, cytosolic tyrosine aminotransferase and mitochondria1 tyrosine aminotransferase in both strains were normal. Activity of 4-hydroxyphenylpyruvic acid dioxygenase was high in IST, but undetectable in III. Urinary excretion of three kinds of tyrosine metabolites (4-hydroxyphenylpyruvic acid, 4 hydroxyphenyllactic acid and 4-hydroxyphenylacetic acid) in the tyrosinemia mice was markedly increased(1). Mating experiments were performed using the III and IST strains. The tyrosine value of F1 was low (<3mg/dl). When the tyrosine values were examined in 75 backcross mice (40 females and 35 males) obtained by mating F1 and III, the ratio of the high (>7mg/dl) to low (<3mg/dl) values was 42 : 33. The ratio of females to males showing high values was 23 : 19 and that showing low values was 17 : 16. 10 backcross mice obtained by mating F1 and IST showed low tyrosine values. In summary, a mouse strain, III, had hypertyrosinemia which showed an autosomal recessive mode of inheritance. The hypertyrosinemia was due to deficiency of 4-hydroxyphenylpyruvic acid dioxygenase, but the node of inheritance of the enzyme deficiency has not yet been tested. Thus the locus has been named provisionally Hpd, 4-hydroxyphenyl pyruvic acid dioxygenase, and the low activity allele found in strain III, as Hpd hty to indicate the hypertyrosinemia. Strain III is a good model for human Type III tyrosinemia(2). REFERENCES 1) Endo, et. al. 1991. Am. J. Hum. Genet. 48:704. 2) Endo, et. al. 1983. Pediatr. Res. 17:92. |
