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Until last year, when the Veterinary Resources Program (VRP) was moved into the Office of Research Services (see "ORS," page 1), only animal models maintained by the NIH Animal Genetic Resource (NIHAGR, see below) were cryopre-served and banked. Since then, however, intramural investigators from NCI, NIMH, NHLBI, NIDDK, NIDR, CBER, and NIA have availed themselves of the service.

William Rall
According to William Rall, a cryobiology physiologist in the VRP, "The primary motivation to bank-down animal models is the NIH policy that new animal models be made available to other investigators. The NIH director very much supports this," he said, answering questions during the NIH Research Festival related to his poster on "The Effect of Genotype on the Efficiency of Mouse and Rat Embryo Cryopreservation and Banking." Several years ago, he noted, Harold Varmus asserted a need for rules for preserving and sharing animal models, and Michael Gottesman, deputy director for intramural research, followed up with a letter so directing the intramural community.

"We have the responsibility," Rall said, "for banking the embryos and distributing them"—a service, he added, that not everyone on campus is aware of. "Investigators reach a point where there's no more room in the animal room, and then they realize they must bank the models they're not using." The place to turn to, of course, is the VRP.

Investigators are "charged by the actual effort," Rall said; donor females are superovulated with the aim of generating large numbers of embryos. "Sometimes only a fraction produce embryos," however, because "the science is imperfect. We can estimate, based on genetic background and experience, whether it will be a problem."

VRP Services

Care and husbandry
Clinical care
Embryo cryopreservation
Environmental enrichment
Facility management
Genetic monitoring
Genetic repository
Health surveillance
Intensive care
Transgenic technology

At the moment, 500 frozen embryos are stored in straws, up to 20 per straw, in a liquid nitrogen refrigerator (at -1960 C) in a building on campus and at a similar facility in Gaithersburg, Maryland. Most are eight-cell mouse embryos; some are rats; and fewer are rabbits. Since 1980, when the Embryo Cryopreservation Program was established, more than 250,000 embryos from 300 mouse, rat, and rabbit genotypes have been cryopreserved and banked.

Cryopreservation is one component of the NIHAGR, which has created "hundreds of animal models for investigators, mostly inbred strains and con-genics (inbred strains carrying spontaneous mutations), and have begun incorporating transgenic and knockout models into the program," Rall said, noting that embryo collection and cryopreser-vation of the poorly reproducing immuno-compromised NIHAGR models is quite challenging.

The NIHAGR serves commercial breeders all over the world, he added: "It's, in effect, an international resource. This means that our investigators can buy from commercial breeders and know that the genetics meets high standards—NIHAGR standards—and that these companies will vary only on service and quality control. The end result is reduced animal costs for NIH," Rall said. Sixty percent of the world's research animals, he added, can trace their ancestors to the NIHAGR colonies.

For more information about VRP cryopreservation services, contact William Rall at 496-0468.

Fran Pollner

In the Beginning....

Carl Hansen
This is where it all begins," said Carl Hansen, drawing an analogy between the NIH Animal Genetic Resource (NIHAGR) and the first chapter of Genesis and noting that his resource colonies provide the breeding stock for 60 percent of all the laboratory animals produced in the United States—and, indeed, the world. He recalled making imaginary site visits to all his stocks about 10 years ago: It was an around-the-world trip that would take several months to complete. He estimated that he sends out 2,000 to 3,000 animals a year to biomedical researchers and commercial breeders..

The FVB/N mouse—the standard background strain for transgenic mice—was "developed here," Hansen said, running through a quick inventory of his wares: "immunodeficient models; models for obesity, diabetes, high blood pressure, arthritis, cancer; models used in behavioral research—mice, rats, some guinea pigs."

An NIHAGR fact sheet boasts a "series of mouse models (that) yields a complete experimental system for T and B lymphocyte as well as natural killer (NK) cell studies" and the "largest collection of genetically defined rats in the world," including a "unique stock of genetically heterogeneous rats developed from a cross of eight inbred strains specifically as a resource for selective breeding studies for behavioral and metabolic traits."

Fran Pollner

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