B6.129S6(C)-Gt(ROSA)26Sor^{tm3(HIF1A*)Kael}/J

Stock number: 009673
Research areas: Research Tools

Description

These LSL-HIF1dPA mice conditionally express a form of hemagglutinin (HA)-tagged human HIF1A (hypoxia inducible factor 1, alpha subunit; HIF1α HIF1dPA) cDNA that escapes recognition by the von Hippel-Lindau tumor suppressor protein by virtue of proline to alanine substitutions. When crossed with a tissue-specific cre strain, excision of a floxed stop cassette enables expression of the cDNA driven by the endogenous mouse Gt(ROSA)26Sor promoter. This strain may be useful in studies of von Hippel-Lindau disease mechanisms.

Detailed description

These LSL-HIF1dPA mice conditionally express a form of hemagglutinin (HA)-tagged human HIF1A (HIF1&alpha, HIF1dPA) cDNA that escapes recognition by the von Hippel-Lindau tumor suppressor protein by virtue of proline to alanine substitutions. When crossed with a tissue-specific cre strain, excision of a floxed stop cassette enables expression of the cDNA driven by the endogenous mouse Gt(ROSA)26Sor promoter. There is no expression until the mice are exposed to Cre recombinase. This strain may be useful in studies of von Hippel-Lindau disease mechanisms.

For example, when crossed to a strain expressing Cre recombinase in liver (see Stock No. 003574), this mutant mouse strain may be useful in studies of VHL disease.

Development

A loxP-flanked neomycin resistance cassette followed by hemagglutinin-tagged human HIF1A cDNA modified with two proline to alanine subsitutions (P402A, P564A) was introduced 3' of the mouse Gt(ROSA)26Sor promoter. The targeting vector was electroporated into 129S6/SvEvTac-derived TC-1 embryonic stem (ES) cells. The line was backcrossed to BALB/c for three generations, then backcrossed four times to C57BL/6 by the donating laboratory.

Allele

Symbol: Gt(ROSA)26Sor^{tm3(HIF1A*)Kael}
Name: targeted mutation 3, William G Kaelin
MGI accession ID: MGI:3832385
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed); Inserted expressed sequence; Humanized sequence
Marker symbol: Gt(ROSA)26Sor
Marker name: gene trap ROSA 26, Philippe Soriano
Chromosome: 6
Strain of origin: 129S6/SvEvTac
Expressed genes: HA,influenza hemagglutinin,; HIF1A,hypoxia inducible factor 1 subunit alpha,human
Molecular note: DNA encoding influenza virus hemagglutinin A- (HA-) tagged human hypoxia-inducible factor 1 alpha (HIF1alpha) with nucleotide substitutions leading to replacement of proline by alanine at amino acid positions 402 and 564 (P402A;P564A), preceded by a floxed neo-STOP cassette, was inserted into the targeted locus. The STOP sequence must be removed by Cre-mediated recombination to allow for expression of the mutated coding sequence. The amino acid substitutions prevent oxygen-dependent prolyl hydroxylation at a.a. position 402 or 564, which is required for binding by von Hippel-Lindau tumor suppressor (VHL).