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.
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 Name||targeted mutation 1, Philip Leder|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Fmn2, formin 2|
|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.|
When maintaining a live colony, heterozygous or wildtype females may be bred to homozygous males. Homozygous males are fertile, while homozygous females are sub-fertile and suffer from recurrent pregnancy loss. Those that do give birth have small litters who tend to die from inadequate nursing.
When using the 129S6-Fmn2tm1Led/RwwJ mouse strain in a publication, please cite the originating article(s) and include JAX stock #016264 in your Materials and Methods section.