129S4.129S2(B6)-Fn1^tm1Hyn/J

Stock number: 008444
Research areas: Cardiovascular Research, Developmental Biology Research

Description

Mice homozygous for the fibronectin 1 (Fn1) targeted mutation die during early embryonic development. Blastocyst development and implantation of homozygotes is normal. Gastrulation is initiated and appears normal, including extensive mesodermal movement. From embryonic day eight onwards homozygous mutant embryos deteriorate through the 10th and 11th days of gestation. Homozygous mutant embryos have a shortened anterior-posterior axes, fail to develop a notochord, somites, or central heart (on the 129S4/SvJae genetic background). Heterozygous mice are viable for at least two years and appear healthy and approximately the same size as wild-type littermates. Plasma levels of fibronectin in heterozygotes are 50% lower than normal wild-type siblings.

Detailed description

Mice homozygous for the Fn1^tm1Hyn targeted mutation die during early embryonic development. Blastocyst development and implantation of homozygotes is normal. Gastrulation is initiated and appears normal, including extensive mesodermal movement. From embryonic day eight onwards homozygous mutant embryos deteriorate through the 10th and 11th days of gestation. Homozygous mutant embryos have a shortened anterior-posterior axes, fail to develop a notochord, somites, or central heart (on the 129S4/SvJae genetic background). Heterozygous mice are viable for at least two years and appear healthy and approximately the same size as wild-type littermates. Plasma levels of fibronectin in heterozygotes are 50% lower than normal wild-type siblings.

In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. This is the case for the strain above. It should be noted that the phenotype could vary from that originally described. On the 129S4 background, the embryos fail to form a central heart. We will modify the strain description if necessary as published results become available.

Development

A PGK-neomycin resistance cassette replaced 0.8 kb of the gene including the translation initiation site and part of the signaling sequence. This mutation was created in 129S2/SvPas-derived D3 embryonic stem (ES) cells. Mixed C57BL/6 and 129S2 mixed background mice were bred to 129S4/SvJae by the donating laboratory for at least 10 generations.

Allele

Symbol: Fn1^tm1Hyn
Name: targeted mutation 1, Richard Hynes
MGI accession ID: MGI:1857170
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Fn1
Marker name: fibronectin 1
Chromosome: 1
Strain of origin: 129S2/SvPas
Molecular note: A PGK-neomycin resistance cassette replaced 0.8 kb of the gene including the translation initiation site and part of the signaling sequence. Plasma concentrations of fibronectin in heterozygotes were one-half those of wild-type littermates. The encoded protein was not detectable in immunoprecipitations from cultures of homozygous mutant E7.5 embryos.