Carries a disruption of the Abcc1a (ATP-binding cassette, sub-family C (CFTR/MRP), member 1a) gene that encodes an ATP-dependent drug-extruding transporter formerly known as Mrp1
Abcc1a encodes ATP-dependent transport proteins for glutathione-, glucuronide-, or sulfate-conjugated substrates, including endogenous compounds such as steroids and leukotrienes as well as xenobiotics drugs
One of a family of ATP-binding cassette genes which encode multi-drug resistance proteins which confers resistance to a range of cytotoxic drugs
Exhibits normal fertility and viability but is deficient in functional MRP1 protein, leading to a 95% reduction in cellular transport of glutathione-conjugated substrates and decreased transport of leukotrienes C4, known inflammatory mediators
Exhibits an impaired inflammatory stimulus response and hypersensitivity to the anti-cancer drug, etoposide and vincristine
Useful for studying the role of ATP-dependent transporters in mediating inflammatory response and to test drug disposition
Genetic Background: FVB Background
The Mrp1 mouse was developed in the laboratory of Piet Borst at the Netherlands Cancer Institute. The model was created by targeting the Abcc1a gene in 129/Ola derived E14 ES cells and injecting the targeted cells into blastocysts. Resultant chimeras were backcrossed to FVB/N for six generations (N6). Taconic received stock in 1999. After additional backcrosses to FVB/NTac to N12, the line was embryo derived. Heterozygotes were intercrossed to generate homozygotes. The colony is maintained through incrossing of homozygous mice.
Wild type for Nnt mutation; carries Pde6brd1 mutation
Wijnholds J, Evers R, van Leusden MR, Mol CAAM, Zaman GJR, Mayer U, Beijnen JH, van der Valk M, Krimpenfort P, Borst P. (1997) Increased sensitivity to anticancer drugs and decreased inflammatory response in mice lacking the multidrug resistance-associated protein.; Nature Med, 3:1275-9.