B6.Cg-Plgrkt^tm1Lmls/J

Stock number: 039532
Product name: Plg-R_KT^-
Research areas: Diabetes and Obesity Research, Immunology, Inflammation and Autoimmunity Research, Internal/Organ Research, Research Tools

Description

These Plg-R_KT^-/- knock-out mice have a neo cassette replacing exons 4-7 of the Plgrkt gene making them useful when studying plasminogen binding and inflammatory macrophage recruitment.

Detailed description

These Plg-R_KT^-/- knock-out mice have a neo cassette replacing exons 4-7 of the plasminogen receptor, C-terminal lysine transmembrane protein, plasminogen receptor KT (Plgrkt) gene. Plgrkt encodes a receptor for 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 the 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, however female homozygotes exhibit growth defects and are unable to lactate. Mice also exhibit increased incidence of dermatitis in a gene dosage-dependent manner, starting at 4 months, with homozygous mice having a 4-fold increase and heterozygous mice having a 2-fold increase compared to controls. The donating investigator suggests that heterozygous mice should be mated together when maintaining a live colony.

Plg-R_KT^-/- mice exhibit a marked defect in macrophage recruitment as well as a reduced plasminogen binding capacity. When fed a high fat diet, Plg-R_KT^-/- mice gain more weight, develop more hepatic steatosis, and are more insulin resistant/glucose intolerant than high fat diet-fed wild type littermates. Macrophage populations exhibit decreased phagocytosis of apoptotic neutrophils in vivo and in vitro and wound closure is significantly delayed during the proliferation phase after burn wounds are induced.

Development

The Plg-R_KT^- targeting vector contains a neomycin resistance (neo) cassette disrupting exons 4-7 (10.42 kb) of the plasminogen receptor, C-terminal lysine transmembrane protein, plasminogen receptor KT (Plgrkt) gene. The construct was electroporated into 129;B6 hybrid embryonic stem (ES) cells and correctly targeted ES cells were injected into blastocysts. The resulting chimeric mice were backcrossed to C57BL/6J mice (Stock No. 000664) for at least 10 generations by the donating investigator. 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.

Allele

Symbol: Plgrkt^tm1Lmls
Name: targeted mutation 1, Lindsey Miles
MGI accession ID: MGI:6384265
Generation method: Targeted
Attributes: Null/Knockout
Synonyms: Plgrkt^tm1Rjpr
Marker symbol: Plgrkt
Marker name: plasminogen receptor, C-terminal lysine transmembrane protein
Marker synonyms: 1110007H22Rik; 5033414D02Rik; AD025; C9orf46; MDS030; Plg-R(KT); PLG-RKT; RGD1306839
Chromosome: 19
Strain of origin: Not Specified
Molecular note: A neomycin resistance cassette replaced exons 4 through 7. Western blot analysis confirmed the absence of protein expression in thioglycollate-elicited macrophages.