These floxed mutant mice possess loxP sites flanking exon 1 of the Vhl gene. This strain may be useful for generating conditional mutations in applications related to hypoxia, von Hippel-Lindau (VHL) disease, and tumor suppression.
Jianping Ye, Pennington Biomedical Research Center
This strain contains loxP sites flanking the Vhl promoter and exon 1. Mice that are homozygous for this allele are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. Cre-mediated recombination results in the deletion of the promoter and exon 1. Studies in which liver-specific inactivation of the Vhl gene was achieved by breeding this strain with albumin promoter driven-Cre mice (see Stock No. 003574 for example) resulted in hemizygous mice that exhibit cavernous hemangiomas of the liver, a rare component of the human von Hippel-Lindau (VHL) disease.
When bred to a strain expressing Cre recombinase in the myeloid cell lineage (see Stock No. 004781 for example), this mutant mouse strain may be useful in studies of myeloid cell mediated inflammation.
When bred to a strain expressing Cre recombinase in liver (see Stock No. 003574 for example), this mutant mouse strain may be useful in studies of the regulation of hypoxia responsive genes.
When bred to a strain expressing Cre recombinase in the kidney and genitourinary tract (see Stock No. 012237 for example), this mutant mouse strain may be useful in studies of genital pathologies associated with VHL disease.
When bred to a strain expressing Cre recombinase in cardiac muscle cells (Tg(Myh6-cre)2182Mds, see Stock No. 011038 for example), this mutant mouse strain may be useful in studies of cardiomyopathy.
When bred to a strain expressing inducible Cre recombinase in the osteoblast lineage (Tg(Sp7-tTA,tetO-EGFP/cre)1Amc), see Stock No. 006361 for example), this mutant mouse strain may be useful in studies of erythropoiesis.
In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. This is the case for the strain above. It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.
A vector containing Vhl exons 1-3 was used to construct the conditional allele. A positive-negative selection cassette, loxP-CMV-hyTK-loxP, was placed 2.6 Kb upstream of exon 1 and a loxP site positioned within intron 1. The targeting vector was electroporated into 129S4/SvJae-derived J1 embryonic stem cells which were subsequently transfected with a cytomegalovirus-driven Cre recombinase plasmid. ES cells in which Cre recombination resulted in exon 1 and the promoter being flanked by loxP sites (the 2-lox allele) were injected into BALB/c blastocysts. The strain was maintained on a C;129S background. The mice were then backcrossed to C57BL/6J for 10 generations. Upon arrival at The Jackson Laboratory, the mice were crossed to C57BL/6J (Stock No. 000664) at least once to establish the colony.
|Allele Name||targeted mutation 1, Rudolf Jaenisch|
|Allele Type||Targeted (Conditional ready (e.g. floxed), No functional change)|
|Allele Synonym(s)||2-lox allele; VHL+f; VHL2; VHLf; Vhlh 2-lox; Vhlh+f; Vhlh2; Vhlh2lox; Vhlhfl|
|Gene Symbol and Name||Vhl, von Hippel-Lindau tumor suppressor|
|Strain of Origin||129S4/SvJae|
|Molecular Note||A CMV-hyTK selection cassette flanked by two loxP sites was inserted approximately 2.6 kb upstream of exon 1. A third loxP site was inserted into intron 1. The hygromycin cassette was deleted in ES cells by transient transfection with a vector driving expression of Cre recombinase. The resulting ES cell derivatives with two loxP sites flanking exon 1 were selected and injected into blastocysts to generate the Vhltm1Jae allele.|
|Mutations Made By|| |
Rudolf Jaenisch, Whitehead Institute, Massachusetts Institute of Technology
When maintaining a live colony, these mice can be bred as homozygotes.
When using the 2-lox allele mouse strain in a publication, please cite the originating article(s) and include JAX stock #012933 in your Materials and Methods section.