IMPC phenotypes (gene matching)
SJL.129(B6)-Nr1i2tm1Sakl/H
| Status | Available to order |
| EMMA ID | EM:04546 |
| International strain name | SJL.129(B6)-Nr1i2tm1Sakl/H |
| Alternative name | SJL/PXR-/- |
| Strain type | Targeted Mutant Strains : Knock-out |
| Allele/Transgene symbol | Nr1i2tm1Sakl |
| Gene/Transgene symbol | Nr1i2 |
Information from provider
| Provider | Matthew Wright |
| Provider affiliation | Institute of Human Genetics, Newcastle University |
| Genetic information | The Nr1i2 (Pxr) gene knock-outs generated by the lab of Kleiwer (Staudinger JL, Goodwin B, Jones SA, Hawkins-Brown D, MacKenzie KI, LaTour A, Liu Y, Klaassen CD, Brown KK, Reinhard J, Willson TM, Koller BH, Kliewer SA. The nuclear receptor PXR is a lithocholic acid sensor that protects against liver toxicity. Proc Natl Acad Sci U S A. 2001 Mar 13;98(6):3369-74) were crossed onto the SJL mouse strain and backcrossed 6 times to generate a Nr1i2 (Pxr) knock-out on an SJL background. By mating a male and female heterozygote from the same litter, a knock-out and wild-type colony were generated. |
| Phenotypic information | Nr1i2 (Pxr, pregnane-X receptor) regulates the inducible expression of the major, drug-metabolising cytochrome P450 3a subfamily of enzymes, which are also responsible for the metabolism of elevated levels of bile acids. Knock-out animals therefore do not respond to inducers such as pregnenolone 16-alpha carbonitrile and show sensitivity to elevated bile acid levels (liver damage). The SJL background shows an unusual constitutively high level of portal tract inflammation (Jones DE, Palmer JM, Kirby JA, De Cruz DJ, McCaughan GW, Sedgwick JD, Yeaman SJ, Burt AD, Bassendine MF. Experimental autoimmune cholangitis: a mouse model of immune-mediated cholangiopathy. Liver. 2000 Oct;20(5):351-6). This strain (along with its wild-type) is therefore a model for examining the effects of drugs and bile acids on portal tract inflammation. |
| Breeding history | Nr1i2 (Pxr) knock-out mice on a C57BL/6 background were bred with SJL mice and progeny backcrossed onto SJL mice 6 times. A male and female from a litter were then mated and homozygous wild-type and knock-out mice used to generate Nr1i2+/+ and Nr1i2-/- colonies. |
| References |
|
| Homozygous fertile | yes |
| Homozygous viable | yes |
| Homozygous matings required | no |
| Immunocompromised | no |
Information from EMMA
| Archiving centre | Mary Lyon Centre at MRC Harwell, Oxford, United Kingdom |
| Animals used for archiving | homozygous 0 |
| Breeding at archiving centre | Males were archived at the time of arrival at the archiving centre. No breeding was performed at the archiving centre. |
Disease and phenotype information
MGI phenotypes (gene matching)
- no phenotypic analysis / MGI
- decreased hepatocyte proliferation / MGI
- abnormal metabolism / MGI
- abnormal enzyme/coenzyme level / MGI
- liver/biliary system phenotype / MGI
- reproductive system phenotype / MGI
- abnormal physiological response to xenobiotic / MGI
- increased physiological sensitivity to xenobiotic / MGI
- decreased physiological sensitivity to xenobiotic / MGI
- impaired behavioral response to xenobiotic / MGI
- mortality/aging / MGI
Literature references
- The PXR is a drug target for chronic inflammatory liver disease.;Wallace Karen, Cowie David E, Konstantinou Dimitrios K, Hill Stephen J, Tjelle Torunn E, Axon Andrew, Koruth Matthew, White Steven A, Carlsen Harald, Mann Derek A, Wright Matthew C, ;2010;The Journal of steroid biochemistry and molecular biology;120;137-48; 20416375