129S1.129(Cg)-Celf4^tm1.1Frk/Frk

Stock number: 018125
Research areas: Mouse/Human Gene Homologs, Neurobiology Research

Description

This strain may be useful for generating spatial and temporal conditional mutants for applications related to genetically complex seizure disorders. Inserted loxP sites flank exon 1 of the Clef4 gene, a brain specific RNA binding protein.

Detailed description

CELF4 (CUGBP, Elav-like family member 4) is a brain specific RNA binding protein. CELF4 has widespread expression in early development, but is limited to the central nervous system in adults. These mutant mice possess loxP sites flanking exon 1 of the (Clef4) gene. Mice that are homozygous for this allele are viable and fertile. When bred to mice that express Cre recombinase, the resulting offspring will have exon 1 deleted in the cre-expressing tissues.

For example, when bred to mice carrying Tg(EIIa-cre)C5379Lmgd (see Stock No. 003724), Cre recombinase expression in the early mouse embryo results in a decreased electroconvulsive threshold (ECT), some homozygote postnatal lethality, and limbic and tonic clonic grand Mal-like seizures in both homozygotes and heterozygotes. The phenotype is more severe on the C57BL/6 background as compared to the 129S1/SvImJ background.

When bred to mice carrying Tg(CAG-(cre/Esr1*)5Amc (Stock No. 004682), tamoxifen-induced Cre-mediated recombination at 7 weeks of age results a decreased ECT and induced as well as spontaneous seizures.

When bred to mice carrying Emx1^tm1(cre)Krj (see Stock No. 005628), Cre recombinase expression in neocortical and hippocampal neurons results in a decreased ECT and handling associated seizures.

When bred to mice carrying Tg(Slc32a1-cre)2.1Hzo (see Stock No. 017535), Cre recombinase expression in in GABAergic neurons results in no significant change in ECT and does not result in a seizure phenotype.

Development

A targeting vector was designed to insert a loxP site 2.1 kb upstream of exon 1 followed by a second loxP site and a frt-flanked neomycin resistance (neo) cassette 444 bp downstream of exon 1. Correctly targeted 129-derived R1 ES cells were injected into C57BL/6J blastocysts and resulting chimeric mice were bred to 129S1/SvImJ mice. Offspring were bred to Tg(ACTFLPe)9205Dym transgenic mice to delete the neo cassette. These mice were backcrossed to 129S1/SvImJ for at least 10 generations.

Allele

Symbol: Celf4^tm1.1Frk
Name: targeted mutation 1.1, Wayne N Frankel
MGI accession ID: MGI:5425629
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed); No functional change
Marker symbol: Celf4
Marker name: CUGBP, Elav-like family member 4
Chromosome: 18
Strain of origin: (129X1/SvJ x 129S1/Sv)F1-Kitl⁺
Molecular note: LoxP sites were inserted 2.1 kb upstream and 444bp downstream of exon 1. An frt-flanked neo selection cassette was deleted from intron 1 in the final allele.