EXPERIMENTAL MODELS

Contributor Information
- Name Malcolm Parker
- Institute Cancer Research UK, London Research Institute: Lincoln's Inn Fields
Tool Details
- Tool name: RIP140 KO Mouse
- Tool type: Experimental models
- Tool sub-type: Mouse
- Disease: Infertility and obesity
- Model: Knock-Out
- Conditional: No
- Genetic background and cross history: Recombinant lambda bacteriophage encompassing an 8.1-kilobase XbaI fragment containing the entire coding region of mouse Nrip1 were isolated from a 129/Sv mouse genomic library. A 3.63-kilobase NsiI fragment containing the entire coding sequence with the exception of the first 27 amino acids was removed and replaced with an internal ribosomal entry site neo cassette from the vector pGT1.8IRESGEOSK. The plasmid DNA was electroporated into 129/Ola embryonic stem embryonic stem cells, and G418-resistant clones were screened for homologous recombination using Southern blot analysis. Of 144 embryonic stem cell clones analyzed, 5 underwent homologous recombination at the Nrip1 locus. Two independent Nrip1-/- clones contributed to the germline and were used to generate Nrip1-null lines.
- Phenotype: Females are infertile and both sexes exhibit a lean phenotype, resistant to high-fat diet-induced obseity and hepatic steatosis.
- Zygosity: Hetero and homozygous mice are viable
- Description: RIP140 is a ligand-dependent corepressor for most nuclear receptors, and functions through interaction with their AF2 activation domains.Scientific objective was to elucidate the function of RIP140 is oestrogen receptor signalling but was subsequently extended to include other nuclear receptors. This mouse maybe useful for studying compounds targeting RIP140 in fertility and obesity associated disorders. Cofactor for nuclear receptors.
- Research area: Cell signaling and signal transduction; Genetics
- Production details: Recombinant lambda bacteriophage encompassing an 8.1-kilobase XbaI fragment containing the entire coding region of mouse Nrip1 were isolated from a 129/Sv mouse genomic library. A 3.63-kilobase NsiI fragment containing the entire coding sequence with the exception of the first 27 amino acids was removed and replaced with an internal ribosomal entry site neo cassette from the vector pGT1.8IRESGEOSK. The plasmid DNA was electroporated into 129/Ola embryonic stem embryonic stem cells, and G418-resistant clones were screened for homologous recombination using Southern blot analysis. Of 144 embryonic stem cell clones analyzed, 5 underwent homologous recombination at the Nrip1 locus. Two independent Nrip1-/- clones contributed to the germline and were used to generate Nrip1-null lines.
- For Research Use Only
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References
- • Nautiyal et al. 2010. Endocrinology. 151(6):2923-32. PMID: 20308529.
- • The nuclear receptor cofactor receptor-interacting protein 140 is a positive regulator of amphiregulin expression and cumulus cell-oocyte complex expansion in the mouse ovary.
- • White et al. 2000. Nat Med. 6(12):1368-74. PMID: 11100122.
- • The nuclear receptor co-repressor nrip1 (RIP140) is essential for female fertility.