Taconic Transgenic Exchange

Bcrp

CONSTITUTIVE KNOCK OUT

Licensing Requirements

FVB Background

Model Number	Zygosity	Nomenclature
2767-F	Homozygous	FVB.129P2-Abcg2^tm1Ahs N7
2767-M	Homozygous	FVB.129P2-Abcg2^tm1Ahs N7

Model Description

Carries a disruption of the Abcg2 gene (ATP-binding cassette, sub-family G, member 2), formerly referred to as Bcrp
Altered drug transport capabilities due to ABC transporter protein deficiency
Bcrp functions as an efficient pharmacological barrier expressed in the apical membrane of epithelial cells of the small intestine, colon, cecum, and renal proximal tubules, in hepatic bile canalicular membranes, in mammary gland alveolar epithelial cells during pregnancy and lactation, and in placental labyrinth cells
Bcrp actively transports various anticancer drugs causing multi-drug resistance when expressed in cancer cells
Homozygote develops phototoxicity upon exposure to pheophorbide a, a chlorophyll metabolite, first expressed as ear lesions and can progress to mice becoming moribund
Homozygotes also displays a novel type of protoporphyria characterized by elevated levels of protoporphrin IX
Useful for studies of ATP-dependent transporters in vivo drug disposition and in inflammatory studies

Origin: The Bcrp mouse was developed in the laboratory of Alfred Schinkel of the Netherlands Cancer Institute in 2002. The model was created by targeting the Abcg2 gene in E14 embryonic stem cells derived from 129P2/OlaHsd mice and injecting the targeted cells into FVB blastocysts. Resultant chimeras were backcrossed to FVB/N for seven generations (N7). Taconic received stock in July 2003. The mice were derived by embryo transfer and are maintained by incrossing of homozygous mice.

Color: Albino

Genetics: Wildtype for Nnt mutation; carries Pde6b^rd1 mutation

Initial Publication: Jonker JW, Buitelaar M, Wagenaar E, Van Der Valk MA, Scheffer GL, Scheper RJ, Plosch T, Kuipers F, Elferink RP, Rosing H, Beijnen JH, Schinkel AH. (2002) The breast cancer resistance protein protects against a major chlorophyll-derived dietary phototoxin and protoporphyria. Proc Natl Acad Sci USA, 99(24):15649-54.

Animal Diet: NIH #31M Rodent Diet

Licensing Requirements:

Label License: Conditions of Use for Taconic Transgenic Models™
Taconic Transgenic Models (Models) are produced and distributed under rights to patents and intellectual property licensed from various institutions. Taconic sells the Models to purchasers, and grants to each purchaser a right under Taconic's rights in such licensed patents and intellectual property to use the purchased Model in consideration of purchasers' acknowledgement of and agreement to the Terms and Conditions of Sale and the following terms of use:

Title to these Models and biological materials derived from them remains with Taconic Farms, Inc
The Models will be used for research purposes only
The Models will not be bred except to obtain embryos or fetuses required for research purposes
The Models and biological materials derived from them will not be distributed to third parties or used for commercial purposes.

Taconic Transgenic Models are produced in Isolated Barrier Unit (IBU™) facilities under MPF™ conditions, and shipped in Taconic Transit Cages (TTC™).