129S6-Fmn2^tm1Led/RwwJ

Stock number: 016264
Research areas: Cell Biology Research, Developmental Biology Research, Reproductive Biology Research

Description

These Fmn2 knockout mice may be useful for studying chromosomal aneuploidy and pregnancy loss.

Detailed description

The proline-rich FH1 domain of the formin 2 (Fmn2) gene was disrupted with a neomycin resistance (neo) cassette, abolishing FH1 domain binding function. Formin 2, a straight-actin-filament nucleator expressed in neurons of the central nervous system, is required for progression through the metaphase of Meiosis I. Specifically, formin 2 controls spindle migration and asymmetric spindle positioning in mouse oocytes. Homozygous males are viable and fertile. Homozygous females suffer from sub-fertility and pregnancy loss. Those that do give birth have small litters that tend to die from inadequate nursing. These mice exhibit arrest of meiosis, lack of spindle formation, and lack polar body extrusion.

Development

A targeting vector was designed to replace 433 amino acids from the proline-rich FH1 domain of the formin 2 (Fmn2) gene with a neomycin resistance (neo) cassette. The construct was electroporated into 129S6/SvEvTac-derived TC-1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts and the resulting chimeric males were bred to 129S6/SvEvTac females. These mice were maintained on a 129S background prior to sending to The Jackson Laboratory Repository. Upon arrival, mice were bred to 129S6/SvEvTac inbred mice for at least one generation to establish The Jackson Laboratory Repository colony.

Allele

Symbol: Fmn2^tm1Led
Name: targeted mutation 1, Philip Leder
MGI accession ID: MGI:2448909
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Fmn2
Marker name: formin 2
Chromosome: 1
Strain of origin: 129S6/SvEvTac
Molecular note: The gene was disrupted by replacement of 1300 bp of the proline-rich exon with a neomycin resistance cassette via homologous recombination, introducing stop codons in all 3 reading frames. The deleted region encodes 433 amino acids and contains the FH1 domain. Northern blot analysis of brain RNA from homozygous mutants confirmed the absence of wild-type gene product. A partial read-through transcript containing the neomycin cassette was observed.