STOCK Tgfb3^tm2(Tgfb1)Vk/J

Stock number: 018624
Research areas: Developmental Biology Research

Description

The Tgfb3 gene is replaced with a Tgfb1 cDNA in these mice, abolishing Tgfb3 expression. TGFB1 expression partially rescues the clefting phenotype associated with Tgfb3 disruption. These mice may be suitable for use in studies examining the isoform-specific roles of transforming growth factors.

Detailed description

In this knock in/out mutant, the transforming growth factor, beta 3 (Tgfb3) coding region was replaced with a transforming growth factor, beta 1 (Tgfb1) cDNA, abolishing Tgfb3 expression. TGFB isoforms are important regulators of cell growth, cell differentiation, apoptosis, and cellular homeostasis. TGFB3 is expressed in the prefusion palatal epithelium and KO models display a cleft of the secondary palate, lung hypoplasia, respiratory distress, hemothorax, and neonatal lethality. When TGFB1 is knocked into the TGFB3 coding region, the clefting phenotype is partially rescued. These mutant mice show partial fusion of the secondary palate. They exhibit a reduction in apoptosis in the midline epithelium during fusion of the palatal shelves, causing anterior and posterior regions of the palate to not fuse. Homozygous mice are viable but do not survive past 2 weeks of age due to failure to feed.

Development

A targeting vector was designed to insert transforming growth factor, beta 1 (Tgfb1) cDNA, followed by a polyadenylation sequence and a loxP-flanked neomycin resistance cassette, into the transforming growth factor, beta 3 (Tgfb3) coding region. The construct was electroporated into (129X1/SvJ x 129S1/Sv)F1-Kitl⁺-derived R1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts and the resulting chimeric males were bred to B6xCBA F1 females to generate a colony of Tgfb1-KI mice. These mice were maintained on a mixed genetic background. Upon arrival at The Jackson Laboratory, mice were bred to C57BL/6J (Stock No. 000664) for at least one generation to establish the colony.

Allele

Symbol: Tgfb3^tm2(Tgfb1)Vk
Name: targeted mutation 2, Vesa Kaartinen
MGI accession ID: MGI:3768675
Generation method: Targeted
Attributes: Null/Knockout; Inserted expressed sequence
Marker symbol: Tgfb3
Marker name: transforming growth factor, beta 3
Chromosome: 12
Strain of origin: (129X1/SvJ x 129S1/Sv)F1-Kitl⁺
Expressed genes: Tgfb1,transforming growth factor, beta 1,mouse, laboratory
Molecular note: A vector containing Tgfb1 cDNA followed by a pgk polyA sequence and a loxP flanked neomycin resistance cassette was inserted into the ATG start site of the targeted gene. Quantitative RT-PCR of RNA isolated from the tips of the palatal shelves demonstrates high Tgfb1 expression but no Tgfb3 expression in homozygotes.