B6N.129S1(Cg)-Hhex^tm2Cwb/J

Stock number: 025396
Product name: Hhex^flox
Research areas: Developmental Biology Research, Internal/Organ Research, Research Tools

Description

Hhex^flox/flox mice may be useful for studying hepatoblast differentiation and intrahepatic bile duct morphogenesis, as well as early lymphoid specification.

Detailed description

These Hhex^flox/flox mutant mice possess loxP sites flanking exons 2-3 of the hematopoietically expressed homeobox (Hhex) gene. HHEX is a transcription factor required for production of all lymphoid lineages and for early development of the liver. Expression is seen in the ventral foregut endoderm at E8.5 and in hepatobiliary tissue during later stages of development. HHEX expression is also evident in adult liver in hepatocytes and biliary epithelial cells in the intrahepatic bile ducts. Mice that are homozygous for this allele are viable and fertile. When bred to mice that express tissue-specific Cre recombinase, resulting offspring will have exons 2-3 deleted in the cre-expressing tissues.

For example, when bred to mice expressing Cre Recombinase in the hepatic diverticulum, resulting offspring were embryonic lethal and had small and cystic livers, absent gall bladders and extrahepatic bile ducts.

When bred to mice expressing Cre Recombinase in the embryonic liver, resulting mice exhibited irregular development of intrahepatic bile ducts, cystic biliary epithelial cells, and a slow, progressive form of polycystic liver disease in adult mice.

Development

A targeting vector was designed to insert a frt-flanked neomycin resistance (neo) cassette followed by a loxP site upstream of exon 2, and a second loxP site downstream of exon 3 of the hematopoietically expressed homeobox (Hhex) gene. The construct was electroporated into 129S1/Sv embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts and resulting chimeric mice were bred with B6.Cg-Tg(ACTFLPe)9205Dym/J transgenic mice (Stock No. 005703) to delete the neo cassette. Progeny were crossed to remove the Flp-expressing transgene, and offspring were bred to C57BL/6NCrl mice for at least 6 generations. Upon arrival, mice were bred to C57BL/6NJ inbred mice (Stock No. 005304) for at least one generation to establish the colony.

Allele

Symbol: Hhex^tm2Cwb
Name: targeted mutation 2, Clifford W Bogue
MGI accession ID: MGI:3721426
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed); No functional change
Marker symbol: Hhex
Marker name: hematopoietically expressed homeobox
Chromosome: 19
Strain of origin: 129S1/Sv
Molecular note: A FRT-flanked neo cassette followed by a loxP site was inserted in the first intron of the targeted gene. An additional loxP site was added downstream of exon 3. Mice were bred to Flpe-expressing mice to excise the neo cassette, leaving exons 2 and 3 flanked by loxP sites.