C57BL/6-Gt(ROSA)26Sor^{tm1(CAG-Plgrkt)Lmls}/J

Stock number: 039534
Product name: CagRosaPlgRKT
Research areas: Immunology, Inflammation and Autoimmunity Research, Internal/Organ Research, Research Tools

Description

CagRosaPlgRKT mice contain a Cre-inducible Plgrkt cDNA inserted into the Gt(ROSA)26Sor locus. These mice are useful when studying plasminogen binding and inflammatory macrophage recruitment.

Detailed description

CagRosaPlgRKT mice contain a Cre-inducible plasminogen receptor, C-terminal lysine transmembrane, plasminogen receptor KT (Plgrkt) cDNA inserted into the Gt(ROSA)26Sor locus. Plgrkt encodes a receptor of plasminogen (Plg), a zymogen synthesized in liver that is activated to generate plasmin (Pla), the major enzyme responsible for fibrin clot degradation in vivo. In addition to fibrinolysis, the Plg/Pla system regulates the recruitment of mononuclear cells during inflammatory response during wound healing. In humans, PLGRKT has been identified as a novel locus for the pathophysiology of childhood obesity and polycystic ovarian syndrome which is associated with obesity, insulin resistance, and type 2 diabetes.

Homozygous mice are viable and fertile.

When bred to CMV-cre mice (Stock No. 006054), the floxed STOP cassette is removed and Plg-R_KT gene expression and protein expression are increased 5-fold and 3.2-fold, respectively, in adipose tissue of resulting Plg-R_KT-OEX mice compared to CagRosaPlgRKT mice. After 10 weeks on a high fat diet, Plg-R_KT-OEX mice have similar body weights as compared to CagRosaPlgRKT mice. Plg-R_KT-OEX mice show improved glucose tolerance and increased insulin sensitivity. Also, Plg-R_KT-OEX mice show a more metabolically favorable body composition phenotype associated with increased energy expenditure and activity, decreased proinflammatory adipose macrophages and decreased inflammation, elevated brown fat thermogenesis, and higher expression of adipose PPARγ and adiponectin.

Development

The CagRosaPlgRKT targeting vector was designed with (from 5' to 3') a ubiquitously expressed CAG promoter, a loxP-flanked stop cassette containing a neomycin resistance (neo) cassette, and plasminogen receptor, C-terminal lysine transmembrane, plasminogen receptor KT (Plgrkt) cDNA sequence followed by a bovine growth hormone polyadenylation signal (BGHpA) and 2xSV40pA sequences. This targeting vector was inserted into the Gt(ROSA)26Sor locus. The construct was electroporated into C57BL/6NTac-derived iTL IC1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts and the chimeric mice were bred to C57BL/6J mice (Stock No. 000664) for at least 10 generations by the donating laboratory (see SNP note below). Upon arrival at The Jackson Laboratory, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL/6J oocytes.

In 2024, a 48 SNP (single nucleotide polymorphism) panel analysis, with 43 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the males sent to The Jackson Laboratory Repository. All 5 markers that determine C57BL/6J from C57BL/6N were found to be C57BL/6N. These data suggest the mice sent to The Jackson Laboratory Repository were on a C57BL/6N genetic background. Since C57BL/6J oocytes were used to establish this live colony, mice are now on a mixed C57BL/6N;C57BL/6J genetic background.

Allele

Symbol: Gt(ROSA)26Sor^{tm1(CAG-Plgrkt)Lmls}
Name: targeted mutation 1, Lindsey Miles
MGI accession ID: MGI:7645446
Generation method: Targeted
Attributes: Inserted expressed sequence
Synonyms: Rosa26 PlgRKT
Marker symbol: Gt(ROSA)26Sor
Marker name: gene trap ROSA 26, Philippe Soriano
Marker synonyms: beta geo; Gtrgeo26; Gtrosa26; R26; ROSA26; SETD5-AS1; Thumpd3as1
Chromosome: 6
Strain of origin: C57BL/6NTac
Molecular note: The targeting vector was designed with (from 5' to 3') a ubiquitously expressed CAG promoter, a loxP-flanked stop cassette containing a neomycin resistance (neo) cassette, and plasminogen receptor, C-terminal lysine transmembrane, plasminogen receptor KT (Plgrkt) cDNA sequence followed by a bovine growth hormone polyadenylation signal (BGHpA) and 2xSV40pA sequences. This targeting vector was inserted into the Gt(ROSA)26Sor locus.