International Mammalian Genome Society

logo18th International Mouse Genome Conference

17-22 October 2004, Seattle, USA


Filipiak WE, Saunders TL

University of Michigan Transgenic Core Facility, Ann Arbor, United States

The rat is an important animal model for cardiovascular, cancer, and pharmacological research. Quantitative trait loci (QTL) associated with these diseases have been mapped in the rat. The application of transgenesis with bacterial artificial chromosomes can refine QTL maps and accelerate the identification of disease genes. Academic transgenic facilities may hesitate to provide transgenic rat services because anecdotal evidence suggests that the production of transgenic rats is less efficient than transgenic mouse production. To compare transgenic efficiency between rats and mice we first established procedures for superovulation and pseudopregnant recipient production. To this end, we compared five different superovulation treatments and four methods of pseudopregnancy induction. The most productive superovulation treatment was 30 IU PMSG followed by 20 IU HCG 48 hours later. The best method to prepare pseudopregnant recipients combined estrus synchronization with LHRH agonist treatment and mating with vasectomized males. These procedures reduced the number of egg donors and the number of rats required pseudopregnant recipient production.

We made three Sprague-Dawley (SD) and one Fischer 344 (F344) transgenic rat models by pronuclear microinjection of DNA. The efficiency of SD transgenesis was one transgenic founder per four egg donors or 1.8% of injected eggs developed into transgenic founders. F344 transgenesis was less efficient: one transgenic founder per fifteen donors or 0.7% of injected eggs developed into founders. In our experience, transgenic efficiency with outbred SD rats is comparable to transgenesis in inbred mouse lines such as FVB/N (one founder per seven donors or 1.0% transgenic eggs) and C57BL/6 (one founder per six donors or 3.3% transgenic eggs). Transgenesis in inbred F344 rats required more effort because of lower egg yields and lower birth rates.

The efficiency of SD rat transgenesis is similar to inbred mice. Transgenic facilities should be encouraged to investigate the feasibility of offering transgenic rat production. Identification of rat lines with desirable superovulation characteristics and birth rates may further improve the efficiency of rat transgenesis in the future.

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