B6;129-Smad1^tm2Sor/J

Stock number: 007613
Research areas: Cell Biology Research, Developmental Biology Research, Internal/Organ Research, Reproductive Biology Research

Description

Homozygotes for the Smad1^tm2Sor (also called Smad1L) allele have abnormal gastic mucosal cell homeostasis and fewer primordial germ cells than wildtype controls. This mutant mouse strain may be useful in studies of stomach development, gastic mucosal homeostasis and BMP and MAPK signaling pathways during development and in the adult.

Detailed description

Homozygotes for the Smad1^tm2Sor (also called Smad1L) allele are viable and fertile, normal in size and do not display any gross physical or behavioral abnormalities. These mice carry a mutation in exon 3, which effects MAPK-mediated phosphorylation of the protein. Western blot analysis of MEFs from homozygotes showed that similar protein levels compared to wildtype. Homozygous embryos have fewer primordial germ cells than wildtype controls. Homozygous mice display abnormal gastric mucosa cell population ratios with fewer zymogenic cells and more parietal cells. The cytoskeleton of MEFs from homozygotes exhibit a loss of adhesion zippers, decreased stress fibers, and an accumulation of actin in the cortical regions with an increase in beta-catenin immunostaining localized to the cell membranes. This mutant mouse strain may be useful in studies of stomach development, gastic mucosal homeostasis and BMP and MAPK signaling pathways during development and in the adult.

Development

A targeting vector containing a floxed PGKneo cassette and a diptheria toxin cassette was used to introduce serine-to-alanine substitutions in the MAPK-consensus phosphorylation sites (S187A, S195A, S206A, S214A) and two conserved phosphoserines in exon 3 (S209 and S210). The construct was electroporated into 129S4/SvJaeSor-derived AK7 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts. The mice were crossed to a strain expressing Cre under the control of the Meox2 promoter to remove the floxed PGKneo cassette. The mice were then crossed to mice carrying the Smad1^tm1Sor mutant allele prior to arriving at The Jackson Laboratory. Upon arrival, mice were bred to C57BL/6J to separate the mutant alleles. These mice carry only the Smad1^tm2Sor (also called Smad1L) mutant allele.

Allele

Symbol: Smad1^tm2Sor
Name: targeted mutation 2, Philippe Soriano
MGI accession ID: MGI:3045219
Generation method: Targeted
Marker symbol: Smad1
Marker name: SMAD family member 1
Chromosome: 8
Strain of origin: 129S4/SvJaeSor
Molecular note: Homologous recombination incorporated serine to alanine substitutions in the MAPK-consensus phosphorylation sites (p.S187A, p.S195A, p.S206A, p.S214A) and two conserved phosphoserines in exon 3 (p.(S209_S210delinsAA)). Western blot analysis of MEF nuclear extracts demonstrated the mutant protein was expressed at similar levels as that of wild-type.