Mammalian Genome

, Volume 8, Issue 2, pp 102–107

A candidate mouse model for Hartnup Disorder deficient in neutral amino acid transport

Authors

  • D. J. Symula
    • McArdle Laboratory for Cancer ResearchUniversity of Wisconsin
    • Laboratory of GeneticsUniversity of Wisconsin
  • A. Shedlovsky
    • McArdle Laboratory for Cancer ResearchUniversity of Wisconsin
  • E. N. Guillery
    • Department of PediatricsUniversity of Wisconsin
  • W. F. Dove
    • McArdle Laboratory for Cancer ResearchUniversity of Wisconsin
    • Laboratory of GeneticsUniversity of Wisconsin
Original Contribution

DOI: 10.1007/s003359900367

Cite this article as:
Symula, D.J., Shedlovsky, A., Guillery, E.N. et al. Mammalian Genome (1997) 8: 102. doi:10.1007/s003359900367

Abstract

The mutant mouse strain HPH2 (hyperphenylalaninemia) was isolated after N-ethyl-N-nitrosourea (ENU) mutagenesis on the basis of delayed plasma clearance of an injected load of phenylalanine. Animals homozygous for the recessive hph2 mutation excrete elevated concentrations of many of the neutral amino acids in the urine, while plasma concentrations of these amino acids are normal. In contrast, mutant homozygotes excrete normal levels of glucose and phosphorus. These data suggest an amino acid transport defect in the mutant, confirmed in a small reduction in normalized values of 14C-labeled glutamine uptake by kidney cortex brush border membrane vesicles (BBMV). The hyperaminoaciduria pattern is very similar to that of Hartnup Disorder, a human amino acid transport defect. A subset of Hartnup Disorder cases also show niacin deficiency symptoms, which are thought to be multifactorially determined. Similarly, the HPH2 mouse exhibits a niacin-reversible syndrome that is modified by diet and by genetic background. Thus, HPH2 provides a candidate mouse model for the study of Hartnup Disorder, an amino acid transport deficiency and a multifactorial disease in the human.

Copyright information

© Springer-Verlag 1997