A xenograft host which lacks liver P450 activity and therefore cannot metabolize most small molecule drugs
Use to get a quick readout on the efficacy of your anticancer lead compounds without first working through PK issues
Replaces use of ABT-treated mice, which can display residual P450 activity and may be limited to short term studies only
Complements data from in vitro testing and permits better selection of which lead compounds to move forward in development
HRN™ stands for Hepatic cytochrome P450 Reductase Null
Mice are homozygous for both the floxed Por allele and the nude mutation and carriers Alb-cre transgene
Exhibits liver-specific conditional disruption of the Por gene; POR is the electron donating enzyme for all cytochrome P450 enzymes
Lacks first pass metabolism by P450 enzymes in the liver and can be used to determine the role of hepatic P450 metabolism in drug disposition
Useful for in vivo efficacy studies using smaller amounts of compound
Can provide information on whether parent or metabolite compounds are responsible for observed efficacy or toxic effects
Offered through a partnership with CXR Biosciences
The HRN™ nude mouse was developed by backcrossing the HRN™ mouse to Taconic's NCr nude strain. The HRN™ mouse was developed in the laboratory of C. Roland Wolf of the Ninewells Hospital & Medical School. The model was created by targeting the Por gene to generate a floxed allele in GK129/1 embryonic stem cells derived from 129P2 mice and injecting the targeted cells into C57BL/6 blastocysts. Resultant chimeras were backcrossed to C57BL/6 for one generation. Mice heterozygous for the floxed Por allele were intercrossed to generate mice homozygous for the floxed Por allele on a mixed B6;129P2 background. The Alb-cre transgene was developed in the laboratory of Mark A. Magnuson at Vanderbilt University School of Medicine by microinjecting Cre recombinase gene under the control of the rat albumin enhancer/promoter into B6D2F2 zygotes. Mice homozygous for the floxed Por allele were bred to carriers for the Alb-cre transgene to generate HRN™ mice. The HRN™ model was backcrossed to C57BL/6J a total of 6 generations (N6). Taconic received stock from CXR Biosciences in April 2007. The mice were backcrossed to C57BL/6NTac (N7) and embryo transfer derived. In 2009, a large scale backcross to the outbred NCr nude strain commenced. After three backcrosses to NCr nudes from representative rotational breeding groups, an intracross was performed. The colony is maintained through rotational outbred mating of females that are homozygous for the floxed Por allele, heterozygous for the nude mutation and carriers for the Alb-cre transgene to males that are homozygous for the floxed Por allele, homozygous for the nude mutation and carriers for the Alb-cre transgene.
Henderson CJ, Otto DME, Carrie D, Magnuson MA, McLaren AW, Rosewell I, Wolf CR. (2003) Inactivation of the hepatic cytochrome P450 system by conditional deletion of hepatic cytochrome P450 reductase
. J Biol Chem 278(15):13480-13486
Note: the publication above describes the HRN™mouse
parent strain. It does not describe the HRN™ nude mouse.
Conditions of Use for HRN™ nude
Title to the Model and biological materials derived from them remains with TACONIC FARMS, INC.
The Model will be used for research purposes only. The Model will not be used in fee-for-service or contract research services.
The Model will not be bred except to obtain embryos or fetuses required for research purposes.
The Model and biological materials derived from them will not be distributed to third parties or used for commercial purposes.