B6.129X1-Twist2^{tm1.1(cre)Dor}/J

Stock number: 008712
Product name: Twist2-
Research areas: Cancer Research, Dermatology Research, Developmental Biology Research, Immunology, Inflammation and Autoimmunity Research, Neurobiology Research, Research Tools

Description

These Twist2-cre (or, Dermo1-cre) mutant mice harbor a Cre recombinase knock-in allele that also abolishes endogenous twist homolog 2 (Drosophila) (Twist2) gene function. They may be useful for Cre-lox applications/Twist2-deficiency research in embryogenesis of mesoderm-derived tissues (including chondrocytes and osteoblasts), as well as NF-kappaB transcription factor/cytokine signaling pathways.

Detailed description

Twist2-cre (or, Dermo1-cre) mutant mice harbor a Cre recombinase "knock-in" allele that also abolishes endogenous Twist2 gene function. Heterozygotes are viable and fertile, while homozygotes (twist-2^-/-) die a few days after birth. Under control of the upstream promoter/enhancer elements, cre expression is observed in a pattern consistent with the wildtype gene; Cre recombinase activity is reported in mesoderm as early as embryonic day 9.5, in mesodermal tissues such as branchial arches and somites, and in condensed mesenchyme-derived chondrocytes and osteoblasts. When heterozygotes are bred with mice containing a loxP-flanked sequence of interest, Cre-mediated recombination will result in deletion of the floxed sequences in Dermo1-expressing tissues of the offspring. Homozygous mice exhibit elevated expression of pro-inflammatory cytokines resulting in perinatal death from cachexia (wasting), as well as progressive growth retardation, impaired movement, thin skin with sparse hair, and severe subcutaneous and internal fat deficiency.

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. It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.

Development

A targeting vector was designed to replace the first exon of the targeted gene with a cre cDNA sequence and an frt-flanked PGK-neo cassette. The construct was electroporated into 129X1/SvJ-derived RW4 embryonic stem (ES) cells. Chimeric mice were bred to C57BL/6J inbred mice to establish the mutant colony. Mutant mice were then bred to FLPe mice (C57 genetic background) to remove the selection cassette. Mice harboring the Dermo1-cre mutation were then backcrossed to C57BL/6J for at least 10 generations prior to arrival at The Jackson Laboratory. Upon arrival, mice were bred to C57BL/6J for at least 1 generation to establish the colony.

Allele

Symbol: Twist2^{tm1.1(cre)Dor}
Name: targeted mutation 1.1, David M Ornitz
MGI accession ID: MGI:3830850
Generation method: Targeted
Attributes: Recombinase-expressing
Marker symbol: Twist2
Marker name: twist basic helix-loop-helix transcription factor 2
Chromosome: 1
Strain of origin: 129X1/SvJ
Expressed genes: cre,cre recombinase,bacteriophage P1
Site of expression: Cre recombinase activity is observed in mesoderm as early as embryonic day 9.5, in mesodermal tissues such as branchial arches and somites, and in condensed mesenchyme-derived chondrocytes and osteoblasts.
Molecular note: A targeting vector was designed to replace the first exon of the targeted gene with a cre cDNA sequence and an frt-flanked PGK-neo cassette. The construct was electroporated into 129X1/SvJ-derived RW4 embryonic stem (ES) cells. Chimeric mice were bred to generate mutant mice. Mutant mice were then bred to FLPe mice (C57 genetic background) to remove the selection cassette.