Carries a disruption of multi-drug resistance genes Abcb1a (ATP-binding cassette, sub-family B (MDR/TAP), member 1A, a.k.a. Mdr1a) and Abcb1b (ATP-binding cassette, sub-family B (MDR/TAP), member 1B, a.k.a Mdr1b) encoding p-glycoprotein 3 and p-glycoprotein 1, respectively
Mdr1a protein is normally expressed actively in the intestine and at the blood-brain and blood-testis barriers
Mdr1b protein is normally highly expressed in the adrenal gland, pregnant uterus and ovaries
These p-glycoproteins actively extrude a wide range of drugs from cells and can confer multi-drug resistance to tumor cells
Lack the protective function of p-glycoproteins and exhibits a functional deficiency in the blood-brain barrier
Useful in a wide range of central nervous system research including neurotoxicology, drug transport, oral bioavailability and multi-drug resistance studies
Genetic Background: FVB Background
The Mdr1a/b mouse was developed in the laboratory of Alfred Schinkel of the Netherlands Cancer Institute. The model was created through sequential targeting of the Abcb1a and Abcb1b genes in E14 ES cells. Resultant chimeras were backcrossed to FVB/N for seven (N7) generations. Taconic received stock in August 1997. The mice were then backcrossed five more generations (N12) to FVB/N. The colony is maintained by mating doubly homozygous mice.
Wild type for Nnt mutation; carries Pde6brd1 mutation
Schinkel AH, Mayer U, Wagenaar E, Mol CA, van Deemter L, Smit JJ, van der Valk MA, Voordouw AC, Spits H, van Tellingen O, Zijlmans JM, Fibbe WE, Borst P. (1997) Normal viability and altered pharmacokinetics in mice lacking mdr1-type (drug-transporting) P-glycoproteins. Proc Natl Acad Sci USA, 94(8):4028-4033.