STOCK Yap1^tm1.1Dupa/J

Stock number: 027929
Product name: Yap^flox
Research areas: Cancer Research, Developmental Biology Research, Internal/Organ Research, Research Tools

Description

The first two exons of the Yap1 gene are flanked by loxP sites in these Yap^flox mice. Cre-mediated excision of the floxed region disrupts transcription of the gene and creates a knockout allele.

Detailed description

Yap1 (yes-associated protein 1; called Yorkie or Yki in Drosophila) encodes an oncoprotein that functions antagonistically with Nf2 (neurofibromatosis 2) to regulate liver development. YAP1 is overexpressed in certain tumors and can transform immortalized mammary epithelial cells in vitro. Overexpression of the protein leads to massive hepatomegaly and rapid progression to hepatocellular carcinoma. Inactivation of Yap1 leads to loss of hepatocytes and biliary epithelial cells in the heterozygous state. Homozygous knockout of the mouse gene results in early embryonic lethality.

The first two exons of the mouse Yap1 gene were flanked by loxP sites to create this Yap^flox strain. Cre-mediated excision of the floxed region disrupts transcription of the gene and creates a knockout allele.

When crossed with Alb-Cre mice (see Stock No. 003574), liver-specific knockouts of the gene can be achieved. Aged compound mutant mice have enlarged, pale livers due to macrovesicular steatosis and progressive fibrosis.

Development

A loxP site was introduced 5’ of exon 1 and an FRT-neomycin-FRT-loxP cassette was introduced to intron 2 through homologous recombination in 129P2/OlaHsd-derived E14TG2a.4 embryonic stem (ES) cells. Resultant mice were crossed with a CMV-FLP recombinase-expressing strain on a C57BL/6 background to excise the neomycin cassette. This leaves exons 1 and 2 flanked by loxP sites. This strain was maintained on a mixed C57BL/6-129 genetic background by the donating lab.

Allele

Symbol: Yap1^tm1.1Dupa
Name: targeted mutation 1.1, Duojia Pan
MGI accession ID: MGI:4819826
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed); No functional change
Marker symbol: Yap1
Marker name: yes-associated protein 1
Chromosome: 9
Strain of origin: 129P2/OlaHsd
Molecular note: A loxP site was inserted upstream of exon 1 and an FRT flanked neo cassette with a 3' loxP site was inserted downstream of exon 2. Flp mediated recombination removed the neo cassette leaving exons 1 and 2 floxed.