STOCK Tbx3^tm1Pa/Mmjax

Stock number: 031491
Product name: Tbx3 null
Research areas: Developmental Biology Research, Endocrine Deficiency Research

Description

This knock-out allele of Tbx3 (T-box 3) carries a deletion of most of the DNA binding T box domain, resulting in embryonic lethality. Homozygous mutant embryos exhibit three major abnormalities: yolk sac cell degeneration, a deficiency of mammary gland induction, and limb defects. This strain may be useful for studying ulnar-mammary syndrome.

Detailed description

The Tbx3 (T-box 3) gene belongs to a family of transcription factors involved in development. Mutations in this gene are associated with ulnar-mammary syndrome and human breast cancer. Exons 2, 2a, and 3, representing most of the DNA binding T-box domain, are deleted in this knock-out allele. Homozygous mutant embryos exhibit three major abnormalities: yolk sac cell death and degeneration at midgestation, a deficiency of mammary gland induction, and forelimb and hindlimb defects. Half of the embryos are dead by E11.5, none survive beyond E16.5. Heterozygote mice do not exhibit limb or mammary gland defects, but do exhibit alterations to external genitalia, including a ventral split in the glans clitoris and a distal bifurcation of the prepuce. In a small number of females, the vagina fails to open. These mice may be useful for studying ulnar-mammary syndrome.

Development

The targeting vector was designed to use a loxP-flanked selection cassette containing HSV-TK and the neomycin resistance gene to delete exons 2, 2a, and 3. These exons encode 158 amino acids of the DNA binding T-box domain. The construct was electroporated into (129X1/SvJ x 129S1/Sv)F1-derived R1 embryonic stem (ES) cells. Correctly targeted ES cells were transiently transfected with a pIC-Cre expression plasmid to delete the neo cassette. The resulting ES cells, with excision of exons 2-3 and the neo cassette, were injected into blastocysts. The resulting chimeric animals were crossed to C57BL/6Tac females. Mice were later crossed to ICR and Swiss Webster outbred mice. The strain was then maintained by sibling mating. Upon arrival, mice were bred to C57BL/6J for at least 1 generation to establish the colony.

Allele

Symbol: Tbx3^tm1Pa
Name: targeted mutation 1, Virginia Papaioannou
MGI accession ID: MGI:2655214
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Tbx3
Marker name: T-box 3
Marker synonyms: D5Ertd189e; TBX3-ISO; UMS; XHL
Chromosome: 5
Strain of origin: (129X1/SvJ x 129S1/Sv)F1-Kitl⁺
Molecular note: A 3.2 kb genomic fragment encompassing 3 exons was replaced with a floxed selection cassette that was subsequently removed in vitro via cre mediated excision. A single loxP site was left in place of exons 2, 2a, and 3, which encoded 158 residues of the T domain.