B6N.129(Cg)-Homer1^tm1Mhd/PfwJ

Stock number: 023312
Research areas: Neurobiology Research

Description

These Homer1 KO mice may be useful for studying the role of HOMER1 on behavioral and neurochemical defects.

Detailed description

These Homer1 KO mice lack exon 2 of homer homolog 1 (Homer1) gene, abolishing gene expression. HOMER1 is a postsynaptic density scaffolding protein expressed in the central nervous system, as well as skeletal muscle, where it mediates the formation of large macromolecular complexes and regulates group 1 metabotrophic glutamate receptor function. Mice that are homozygous for this allele are viable and fertile. These mice exhibit myopathy characterized by decreased muscle fiber cross-sectional area and decreased skeletal muscle force generation. They display mild somatic growth retardation, poor motor coordination, enhanced sensory reactivity and learning deficits, and an increase in sensitivity to cocaine-induced locomotion and conditioned reward. They also display behavioral and neurochemical abnormalities consistent with the schizophrenia including decreased radial arm maze performance, impaired prepulse inhibition, enhanced behavioral despair, increased anxiety in a novel objects test, enhanced reactivity to novel environments, decreased instrumental responding for sucrose and enhanced methamphetamine-stimulated motor behavior.

Development

A targeting vector was designed to insert a single loxP site upstream of exon 2, and a second loxP site, followed by a frt-flanked neomycin resistance (neo) cassette, downstream of exon 2 of the homer homolog 1 (Homer1) gene. The construct was electroporated into (129X1/SvJ x 129S1/Sv)F1-Kitl⁺-derived R1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts and resulting chimeric mice were bred to C57BL/6N mice. These mice were bred to C57BL/6N mice for at least 5 generations. These mice also carried a Homer2^tm1Mhw KO allele. Upon arrival at The Jackson Laboratory, mice were bred to C57BL/6NJ (Stock No. 005304) for at least one generation to establish the colony. The Homer2^tm1Mhw was bred out and is maintained separately as Stock No. 023313.

Allele

Symbol: Homer1^tm1Mhd
Name: targeted mutation 1, Marlin H Dehoff
MGI accession ID: MGI:3526529
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Homer1
Marker name: homer scaffolding protein 1
Chromosome: 13
Strain of origin: (129X1/SvJ x 129S1/Sv)F1-Kitl⁺
Molecular note: One loxP site was inserted 200 bp upstream of exon 2 and an SV40-neo cassette flanked with frt sites and containing an additional loxP site was inserted 700 bp downstream of exon 2. The neomycin insert was subsequently removed by crossing to Flpe transgenic mice after which exon 2 was excised by crossing to CMV-cre transgenic mice.