STOCK Chn1^tm1.1Schei/J

Stock number: 026751
Research areas: Developmental Biology Research, Neurobiology Research, Research Tools

Description

Chn1^flox mice may be useful for studying cortical and spinal motor circuits.

Detailed description

Chn1^flox mice possess loxP sites flanking exons 2-3 of the chimerin 1 (Chn1) gene. CHN1 is a GTPase-activating protein for the receptor tyrosine kinase EphA4, which is predominantly expressed in neurons and is involved in controlling multiple axonal guidance steps, most prominently in the locomotor circuits. Chimerin 1 plays an important role in neuronal signal-transduction mechanisms and ocular motor axon pathfinding. Mutations in this gene are associated with Duane's retraction syndrome 2, which is characterized by limited outward movement of the affected eye. This is caused by miswiring of the eye muscles or misdirected or absent ocular nerves. Mice that are homozygous for this allele are viable and fertile. When bred to mice that express tissue-specific Cre recombinase, resulting offspring will have exons 2-3 deleted in the cre-expressing tissues.

For example, when bred to B6.C-Tg(CMV-cre)1Cgn/J mice (Stock No. 006054), resulting Chn1 KO mice resulting offspring exhibit a rabbit-like hopping gait with synchronous hindlimb movements, similar to that seen in EphA4 KO mice.

Development

A targeting vector was designed to insert a loxP site upstream of exon 2 followed by a frt-flanked neomycin resistance (neo) cassette, and a second loxP site downstream of exon 3 of the chimerin 1 (Chn1) gene. The construct was electroporated into 129SvEvTac embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts and resulting chimeric mice were bred. Offspring were bred with Flp transgenic mice to delete the neo cassette, and progeny were crossed to remove the Flp-expressing transgene. Chn1^flox mice were bred to C57BL/6J mice for at least 5 generations. Upon arrival, mice were bred to C57BL/6J inbred mice (Stock No. 000664) for at least one generation to establish the colony.

Allele

Symbol: Chn1^tm1.1Schei
Name: targeted mutation 1.1, Peter Scheiffele
MGI accession ID: MGI:5614296
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed); No functional change
Marker symbol: Chn1
Marker name: chimerin 1
Chromosome: 2
Strain of origin: 129S6/SvEvTac
Molecular note: A targeting vector was designed to insert a loxP site upstream of exon 2 followed by a frt-flanked neomycin resistance (neo) cassette, and a second loxP site downstream of exon 3 of the gene. FLP mediated recombination removed the FRT-flanked neo cassette leaving exons 2 through 3 floxed.