STOCK Hap1^tm1Xjl/J

Stock number: 007749
Research areas: Cell Biology Research, Developmental Biology Research, Mouse/Human Gene Homologs, Neurobiology Research, Research Tools

Description

These huntingtin-associated protein-1 (HAP1) mutant mice may be useful in studying hypothalamic neurodegeneration and the loss of body weight in Huntingon's disease (HD), neurotransmitters, microtubule-dependent transporters, intracellular trafficking, receptor tyrosine kinase and neurite function, and feeding.

Detailed description

Mice homozygous for this Huntingtin Associated Protein (HAP1)-deficient allele have neurodegeneration in areas of the hypothalamus that control feeding behavior, resulting in decreased feeding behavior, dehydration, hypoactivity, and death between two and 15 days after birth. No protein expression from the targeted gene is observed in brain tissue from homozygous mice. Hypothalamus tissue from HAP1-deficient homozygotes exhibit reduced levels of gamma-aminobutyric acid-A (GABA_A; a neurotransmitter associated with feeding) and tropomyosin-related kinase A receptor tyrosine kinase (TrkA; a nerve growth factor receptor associated with neurite outgrowth). Heterozygous mice are viable and fertile with no abnormalities in HAP1 expression levels, life span, behavior, and body weight. These huntingtin-associated protein-1 (HAP1) mutant mice may be useful in studying the hypothalamic neurodegeneration and loss of body weight in Huntingon's disease (HD), neurotransmitters, microtubule-dependent transporters, intracellular trafficking, receptor tyrosine kinase and neurite function, and feeding.

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. These mice were originally published on a mixed Black Swiss and 129S6/SvEvTac genetic background. It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.

Development

A targeting vector was designed to replace the first two exons (first 131 amino acids) of the targeted gene with a neomycin cassette. The construct was electroporated into 129S6/SvEvTac-derived TC-1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient C57BL/6 blastocysts. The resulting chimeric males were bred with Black Swiss females to generate mutant offspring. These HAP1 mutant mice were maintained on a mixed genetic background ("129S6Ev/Black Swiss" and possibly "SV129BL/6") for many generations prior to arrival at The Jackson Laboratory. Upon arrival at The Jackson Laboratory, these mice may have been bred to C57BL/6J inbred mice (Stock No. 000664) for at least one generation to establish the colony.

Allele

Symbol: Hap1^tm1Xjl
Name: targeted mutation 1, Xiao-Jiang Li
MGI accession ID: MGI:2670598
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Hap1
Marker name: huntingtin-associated protein 1
Chromosome: 11
Strain of origin: 129S6/SvEvTac
Molecular note: Exons 1 and 2, which encode the first 131 amino acids, were replaced with a neomycin selection cassette. Protein was undetected in the brains of homozygous mutant mice by Western blot analysis.