Carries a disruption of multi-drug resistance genes Abcb1a (ATP-binding cassette, sub-family B (MDR/TAP), member 1A, a.k.a. Mdr1a) encoding p-glycoprotein 3
Mdr1a protein is expressed actively in the intestine and at the blood-brain and blood-testis barriers
p-glycoprotein 3 actively extrudes a wide range of drugs from cells and can confer multi-drug resistance to tumor cells
Lack the protective function of p-glycoprotein 3 and exhibits a functional deficiency in the blood-brain barrier
Useful in neurotoxicology, drug transport, chemotherapy, multi-drug resistance and oral bioavailability research
Susceptible to developing a severe, spontaneous intestinal inflammation phenotypically similiar to human inflammatory bowel disease (IBD)
Genetic Background: FVB Background
The Mdr1a mouse was developed in the laboratory of Alfred Schinkel of the Netherlands Cancer Institute. The model was created by targeting the Abcb1a gene in E14 ES cells. Resultant chimeras were backcrossed to FVB for seven (N7) generations. Taconic received stock in 1994 and derived the line by Caesarean transfer. The colony is maintained by incrossing homozygous mice.
Wildtype for Nnt mutation; carries Pde6brd1 mutation
Schinkel AH, Smit JJM, van Tellingen O, Beijnen JH, Wagenaar E, van Deetmer L, Mol CAAM, van der Valk MA, Robanus-Maandag BC, te Tiele HPJ, Berns AJM, Borst P. (1994) Disruption of the Mouse mdr1a P-Glycoprotein Gene Leads to a Deficiency in the Blood Brain Barrier and to Increased Sensitivity to Drugs. Cell, 77:491-502.