These Soat2 knock-out mice lack cholesterol ester synthesis in liver and intestine, and are resistant to diet-induced hypercholesterolemia and cholesterol gallstone formation.
Robert V Farese, Jr., Harvard University School of Public Health
Mice that are homozygous null for this targeted mutation are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. Southern blot analysis and RT-PCR indicated the targeted gene was disrupted. These mice lack cholesterol ester synthesis in liver and intestine and are resistant to diet-induced hypercholesterolemia and cholesterol gallstone formation. In homozygous mice fed regular diet, acyl CoA: cholesterol acyltransferase (ACAT) enzyme activity was reduced by 92% in intestine, and by 99% in liver. Homozygous mice fed high-fat/high cholesterol diet had low ACAT activity. Although ACAT2 deficient mice absorb less cholesterol than wild-type mice when fed a high fat/ high cholesterol diet, histological examination indicated enterocytes in the mutant mice were normal. This mutant mouse strain represents a model that may be useful in studies related to human resistance to diet-induced hypercholesterolemia and cholesterol gallstone formation.
A targeting vector containing approximately 1.5 kb Soat2 sequence, neomycin resistance, and herpes simplex virus thymidine kinase genes was utilized in the construction of this mutant. The Soat2 sequence targeted in the construct corresponded to the carboxy terminal and 28% of the ACAT2 protein. The construct was electroporated into 129S4/SvJae derived RF8 embryonic stem (ES) cells. Selected ES cells were then used to generate mice.
|Allele Name||targeted mutation 1, Bob Farese|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Soat2, sterol O-acyltransferase 2|
|Strain of Origin||129S4/SvJae|
|Molecular Note||The gene was disrupted by replacement of 1.5 kb of 3' sequences with a neomycin resistance cassette by homologous recombination. The gene targeting event results in deletion of 28% of the protein coding sequence. Absence of gene expression in homozygous mutant animals was confirmed by RT-PCR analysis of mRNA from liver and small intestines.|
|Mutations Made By|| |
Robert Farese, Jr., Harvard University School of Public Health
Coat color expected from breeding:Black
When using the ACAT2 KO mouse strain in a publication, please cite the originating article(s) and include JAX stock #004185 in your Materials and Methods section.