In this strain, the cytochrome P450, family 8, subfamily b, polypeptide 1 (Cyp8b1) gene is replaced with a β-galactosidase (lacZ) sequence and a neomycin resistance (neo) cassette in reverse orientation, abolishing gene expression. Cyp8b1 is expressed in the liver and is required for the synthesis of the bile acid, cholic acid. Cholic acid is required for the absorption of dietary long-chain fatty acids and cholesterol in the intestine, and in the liver suppresses endogenous bile acid synthesis. Cyp8b1 KO mice fail to produce cholic acid, have increased bile acid synthesis, and reduce the absorption of dietary lipids. Homozygotes are viable and fertile.
A targeting vector was designed to replace the entire coding region of the cytochrome P450, family 8, subfamily b, polypeptide 1 (Cyp8b1) gene with a β-galactosidase (lacZ) sequence and a neomycin resistance (neo) cassette in reverse orientation. The construct was electroporated into 129S7/SvEvBrd-Hprt+-derived AB1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts and the resulting chimeric males were bred to C57BL/6J females. These mice were maintained on a mixed C57BL/6J;129 background. Upon arrival at The Jackson Laboratory, mice were bred to C57BL/6J (Stock No. 000664) for at least one generation to establish the colony.
|Allele Name||targeted mutation 1, David Russell|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Cyp8b1, cytochrome P450, family 8, subfamily b, polypeptide 1|
|Strain of Origin||129S7/SvEvBrd-Hprt+|
|Molecular Note||The coding region was replaced with beta-galactosidase coding sequence and a neomycin resistance gene in reverse orientation. Transcript was not detected in livers of mutant mice.|
|Mutations Made By|| |
Dr. David Russell, Univ of Texas Southwest Med Ctr Dallas
When maintaining a live colony, homozygous mice may be bred together.
When using the B6;129S7-Cyp8b1tm1Rus/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #018771 in your Materials and Methods section.