| Research Abstract |
We have clone cDNA for human, mouse and porcine 4-hydroxyphenylpyruvate dioxygenase from cDNA libralies constructed from mRNA of human, mouse and porcine liver respectively, Using human and mouse cDNA as proves, we obstained DNA fragments containing exons of HPD from human and mouse genomic libraries, Through these studies we have clarified the structure of human and mouse HPD gene. Similarly, we have elucidated the structures of cDNA and gene for human fumarylacetoacetase.
Based on these progress we analyzed gene mutations in human FAH gene from a Japanese patient with type 1 tyrosinemia and mouse HPD gene from III mouse, a tyrosinemic mouse.These studies revealed mutations on FAH gene and HPD gene, respectively.
Using abino lethal mouse which is defective for Fah, and III mouse which is defective for HPD,we generated mice which carry both mutation, one on FAH gene and one on HPD gene. Fah deficient mice were neonatally lethal but these double mutants were vaiable, indicating that defective HPD gene rescues the lethal phenotype of albino deletion mouse.
Futher, we constructed recombinant adenovirus which express human HPD.In cultured cells, transduction of the recombinant virus effectively expresses human HPD.This recombinant virus will be useful to express human HPD in experimental animals.
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