B6;129P2-Has2^tm1Jam/J

Stock number: 007226
Research areas: Cancer Research, Cardiovascular Research, Cell Biology Research, Developmental Biology Research, Internal/Organ Research, Research Tools

Description

These Has2 mutant mice may be useful in studying embryogenesis and development, specifically cardiac and vascular morphogenesis, as well as cell transformation.

Detailed description

While heterozygous mice are viable and fertile, mice homozygous for this targeted allele die between embryonic day (E)9.5 and E10.5. Embryonic mRNA expression from the targeted gene shows only truncated transcripts of the expected length, with no full-length mRNA expression. Homozygous embryos exhibit severe cardiac and vascular abnormalities, lack hyaluronan (HA), and have yolk sac and somite deformities. Heart deformities can be rescued in explants from homozygous mice following exogenous HA or activated H-Ras treatment. These Has2 mutant mice may be useful in studying embryogenesis and development, specifically cardiac and vascular morphogenesis, as well as cell transformation.

Development

A targeting vector was designed to replace a portion of intron 3 (including the splice acceptor) and the first 60 codons of exon 4 (encoding part of the cytoplasmic catalytic domain) of the targeted gene with a PGK-Neo cassette in reverse orientation. The construct was electroporated into 129P2/OlaHsd-derived GK129 embryonic stem (ES) cells. Correctly targeted ES cells were microinjected into C57BL/6J blastocysts, and chimeric offspring were bred to C57BL/6J mice. Heterozygous mutants were maintained on this mixed genetic background for many generations prior to arrival at The Jackson Laboratory. Upon arrival, these mice were bred to C57BL/6J inbred mice for at least one generation to establish the colony.

Allele

Symbol: Has2^tm1Jam
Name: targeted mutation 1, John A McDonald
MGI accession ID: MGI:2386077
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Has2
Marker name: hyaluronan synthase 2
Chromosome: 15
Strain of origin: 129P2/OlaHsd
Molecular note: The gene was disrupted by replacement of the end of intron 3 and the first 60 codons of the cytoplasmic catalytic domain containing exon 4 with a PGK-neo cassette via homologous recombination. Homozygous mutant embryos were observed at days E9.5-E11.5 and RT-PCR analysis of embryonic mRNA detected truncated mutant transcripts.