B6.BTBR-Pah^enu2/MalnJ

Stock number: 029218
Product name: B6 Pah^enu2
Research areas: Metabolism Research, Mouse/Human Gene Homologs, Neurobiology Research

Description

Pah^enu2 mice on a C57BL/6J congenic background may be useful when studying phenylketonuria (PKU).

Detailed description

Homozygous mutant mice display severe hyperphenylalaninemia and other hallmarks of phenylketonuria (PKU) when not maintained on a phenylalanine-free diet. Hyperphenylalaninemia leads to progressive neurological symptoms and seizures. Mice are hypopigmented on a standard diet. Homozygous females and males are viable, however homozygous females with PKU will not rear their young when maintained on a standard mouse diet.

It has been the experience of colonists at The Jackson Laboratory (2022) that some mice develop cloudy eyes and enlarged eyes. Histology reports note lens rupture leading to anterior uveitis, closure of the drainage angle due to anterior synechia, segmental degeneration of the ganglion cell layer consistent with glaucoma.

In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. It should be noted that the phenotype of these C57BL/6J-congenic mice could vary from that originally described on a BTBR genetic background. We may modify the strain description if necessary as published results become available.

Development

Pah^enu2 mice were developed in the laboratory of Dr. Alexandra Shedlovsky at the McArdle Laboratory for Cancer Research, University of Wisconsin. The mutation was generated by ENU treatment of BTBR +^T tf/tf males and progeny were selected for severe hyperphenylalaninemia. A T835C missense mutation in exon 7 of the phenylalanine hydroxylase (Pah) gene results in a phenylalanine to serine substitution at amino acid 263 (F263S). These mice, on BTBR background, are available as Stock No. 002232. Dr. Michael Allen (University of North Texas Health Science Center) backcrossed these mice to C57BL/6J mice (Stock No. 000664) for many generations to make this congenic stock JR 029218. Upon arrival, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL/6J oocytes. The tf/tf allele was bred out of the colony.

Allele

Symbol: Pah^enu2
Name: phenylalanine hydroxylase enu 2
MGI accession ID: MGI:1857272
Generation method: Chemically induced (ENU)
Synonyms: HPH5.1
Marker symbol: Pah
Marker name: phenylalanine hydroxylase
Marker synonyms: PH; PKU; PKU1
Chromosome: 10
Strain of origin: BTBR
Molecular note: A c.788T>C mutation in exon 7 results in a phenylalanine to serine substitution at amino acid 263 (p.F263S).