C3Fe.129(Cg)-Fig4^tm1.1Mm/J

Stock number: 039611
Product name: Fig4^flox
Research areas: Mouse/Human Gene Homologs, Neurobiology Research, Research Tools

Description

Fig4^flox mice possess loxP sites flanking exon 4 of the FIG4 phosphoinositide 5-phosphatase (Fig4) gene. These mice may be useful for studying Charcot-Marie-Tooth disease type 4J.

Detailed description

FIG4, a lipid phosphatase, contains a CX₅RT phosphatase active site and catalyzes removal of a phosphate from PI(3.5)P2, a membrane-bound phospholipid involved in the trafficking and fusion of intracellular vesicles. Mutations in human FIG4 are associated with Charcot-Marie-Tooth disease type 4J (CMT4J), Yunis-Varón syndrome, and a rare form of ALS. These Fig4^flox mice harbor loxP sites flanking exon 4 of the FIG4 phosphoinositide 5-phosphatase (Fig4) gene.

Homozygous Fig4^flox mice are viable and fertile with no overt phenotype. When bred to mice that express tissue-specific Cre recombinase, resulting offspring will have exon 4 deleted in the cre-expressing tissues. The donating laboratory bred these Fig4^flox to a ubiquitously expressing E2a-Cre mouse line (Stock No. 003724) and found that resulting progeny reproduced the phenotype of Fig4 null mice, including small size, tremors and early lethality. These Fig4^flox mice may be useful in studies of Charcot-Marie-Tooth disease type 4J.

Development

The Fig4^flox targeting vector was designed to insert loxP sites flanking exon 4 of the FIG4 phosphoinositide 5-phosphatase (Fig4) gene on chromosome 10. The targeting construct contained 2.6 kb of upstream sequence from intron 3, 1.7 kb of downstream sequence from intron 4 and an Frt-flanked neomycin (neo) cassette. The construct was electroporated into (129X1/SvJ x 129S1/Sv)F1-Kitl⁺-derived R1 embryonic stem (ES) cells and correctly targeted ES cells were injected into recipient blastocysts. The resulting chimeric mice were bred with mice expressing a FLP recombinase, on an unknown genetic background, to remove the neo cassette. The resulting Fig4^flox mice, with neo cassette removed and floxed exon 4 intact, were backcrossed to C3HeB/FeJ (Stock No. 000658) mice for at least 10 generations by the donating laboratory. Upon arrival at The Jackson Laboratory, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize C3HeB/FeJ oocytes.

Allele

Symbol: Fig4^tm1.1Mm
Name: targeted mutation 1.1. Miriam H Meisler
MGI accession ID: MGI:5431009
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed); No functional change
Synonyms: Fig4^flox
Marker symbol: Fig4
Marker name: FIG4 phosphoinositide 5-phosphatase
Marker synonyms: A530089I17Rik; ALS11; BOP; BTOP; CMT4J; dJ249I4.1; KIAA0274; RGD1311375; Sac3; YVS
Chromosome: 10
Strain of origin: (129X1/SvJ x 129S1/Sv)F1-Kitl⁺
Molecular note: A loxZP site was inserted upstream of exon 4 and another loxP site was placed downstream along with an FRT flanked neo cassette immediately 3'. Th neo cassette was subsequently removed by crossing to flp expressing mice. No protein product was detected by Western blot in exon 4 deleted mice.