Abstract
Ethylnitrosourea mutagenesis of spermatogonial stem cells and a three-generation breeding scheme were used to screen for recessive mutations that cause defects in phenylalanine metabolism leading to elevated serum levels of this amino acid. This paper describes the isolation of such a mutation, hph-1, causing a heritable hyperphenylalaninemia in the neonate and weanling and an inability to effectively clear a phenylalanine challenge in the adult. Micro-pedigree analysis of the original mutant mouse and data obtained from crosses of affected and unaffected animals indicate that the mutation segregates in an autosomal recessive manner. An interspecies mouse backcross mapping experiment places the mutant gene locus on mouse chromosome 14 very near Np-1 and a backcross experiment with a conventional inbred mouse strain involving a nearby locus confirms the chromosome 14 assignment. The initial symptomatology of the mutant phenotype suggests this mutant may represent a useful animal model for the study of hyperphenylalaninemia in man.