In this Cd36 knockout strain, a range of lipid-related metabolic traits are observed: reduced preference for food rich in fat, altered fatty acid uptake and lowered food intake. They may be useful in studies of taste preference, glucose metabolism, lipid homeostasis, hemostasis, thrombosis, malaria, inflammation, and atherogenesis.
Maria Febbraio, Cleveland Clinic
CD36 is a class B scavenger receptor that is involved in fatty acid and glucose metabolism, heart disease, gustatory taste of lipid/fat, and lipid metabolism. CD36 also functions as a microglial surface receptor for amyloid beta peptide. These mutant mice carry a targeted mutation in which exon 3, which encodes the first 40 amino acids and the translation initiation site, is replaced by a NEO cassette (in opposite orientation). Mice that are homozygous for the targeted mutation are viable and fertile, but smaller in size than controls. No gene product (protein) is detected by immunoprecipitation or Western blot analysis of fat, muscle, heart, macrophages, liver, and endothelial cells from homozygotes. Homozygotes eat less and have a reduced preference for food rich in fat. Mutant homozygous mice exhibit increased plasma ketone (beta hydroxybutyrate) and circulating HDL cholesterol levels; elevated fasting levels of nonesterified free fatty acids, and triacylglycerol; and decreased fasting blood glucose levels, when compared to controls. Uptake of fatty acids is decreased in muscle, heart and adipose tissue in homozygotes. IgM levels and transitional B cells in spleen and bone are increased in homozygotes. The increase in cerebral blood flow induced by amyloid-beta peptide is absent in homozygotes. Following experimentally induced injury, regenerating nerves have thinner myelination and more macrophages present than seen in controls. The resting coronary resistance blood pressure is lower in homozygotes than in controls.
While at Weill Medical College (Cornell University), Dr. Maria Febbraio designed a targeting vector containing a NEO cassette in opposite transcription orientation was used to disrupt exon 3, encoding the first 40 amino acids and the translation initiation site. The construct was electroporated into 129S1/Sv-Oca2+ Tyr+ Kitl+ derived CJ7 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts. The resulting male chimeric animals were crossed to C57BL/6 mice. 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, Maria Febbraio|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||Cd36-; CD36 KO; CD36KO; FAT/CD36-|
|Gene Symbol and Name||Cd36, CD36 molecule|
|Strain of Origin||129S1/Sv-Oca2+ Tyr+ Kitl+|
|Molecular Note||A neomycin cassette replaced a 1kb fragment including the transcription start site.|
|Mutations Made By|| |
Maria Febbraio, Cleveland Clinic
When maintaining a live colony, these mice can be bred as homozygotes.
When using the CD36 KO mouse strain in a publication, please cite the originating article(s) and include JAX stock #019006 in your Materials and Methods section.