These floxed mutant mice possess loxP sites flanking exon 2 of the Mbtps1 gene. This strain may be useful for generating conditional mutations in studies of lipid homeostasis, cholesterol and fatty acid metabolism, and sterol regulatory element-binding protein (SREBP) activation pathways.
Dr. Jay D. Horton, Univ of Texas SW Med Center at Dallas
These mice carry a targeted mutation in which exon 2 of the targeted gene is flanked by loxP sites. A loxP-flanked ("floxed") neomycin resistance cassette also is inserted downstream in intron 2. Homozygotes are viable and fertile, and the floxed gene appears to function normally. When homozygotes are crossed with transgenic strains expressing Cre-recombinase, cre-mediated recombination of the loxP-flanked sequences can result in one of three genotypes: a) deletion of the neo cassette only, leaving a loxP-flanked second exon and unimpaired endogenous gene function. b) Deletion of exon 2 only, leaving a loxP-flanked neo cassette and no endogenous gene function. c) Deletion of both the neo cassette and exon 2, leaving a single loxP site and no endogenous gene function. When these floxed mutant mice are bred to mice carrying the Mx1-cre transgene (for example, Stock No. 003556), liver-specific disruption of the endogenous gene in Mx1-cre positive, floxed homozygotes leads to reduced expression of genes involved in cholesterol and fatty acid synthesis. Germline disruption of the endogenous gene results in early embryonic lethality. These floxed mutant mice may be useful in studies of lipid homeostasis, cholesterol and fatty acid metabolism, and SREBP activation pathways.
When bred to a strain expressing Cre recombinase in chrondocytes (see Stock No. 003554 for example), this mutant mouse strain may be useful in studies of cartilage and bone development.
A targeting vector was generated containing a single loxP site within intron 1 and a loxP-flanked neomycin resistance cassette within intron 2 of the endogenous gene (loxP-exon2-loxP-Neo-loxP). This construct was electroporated into 129S6/SvEvTac-derived SM-1 embryonic stem (ES) cells. Correctly targeted cells were injected into C57BL/6 blastocysts. Chimeric males were bred to C57BL/6J females and the heterozygous offspring were bred to facilitate the line (S1Pflox). S1Pflox mice were next bred with Mx1-cre transgenic mice on a mixed C57BL/6J;SJL background. Transgenic positive mice also homozygous for the targeted mutation were interbred for an unknown number of generations before arrival at The Jackson Laboratory. Upon arrival, mice were selectively bred for the targeted mutation (and against the transgene), resulting in homozygous Mbtps1 mutant mice.
|Allele Name||targeted mutation 1, Jay D Horton|
|Allele Type||Targeted (Conditional ready (e.g. floxed), No functional change)|
|Gene Symbol and Name||Mbtps1, membrane-bound transcription factor peptidase, site 1|
|Site of Expression||liver|
|Strain of Origin||129S6/SvEvTac|
|Molecular Note||A loxP site was inserted into intron 1 and a loxP-flanked neomycin selection cassette was inserted into exon 2.|
|Mutations Made By|| |
Dr. Jay Horton, Univ of Texas SW Med Center at Dallas
When maintaining a live colony, mice homozygous for the targeted mutation are bred.
When using the S1P floxed mouse strain in a publication, please cite the originating article(s) and include JAX stock #005994 in your Materials and Methods section.