JAX Notes October 15, 1989

Retired breeder mice: a useful animal model

Retired breeders are suitable research animals

Retired breeder mice are mature mice that are beyond the age of peak reproductive performance. However, this does not preclude retired breeders from being suitable research mouse models for certain types of studies. For example, retired breeders are good sources of blood or tissues for in vitro assays, if the outcome of the assay will not be influenced by the reproductive status of the mouse.

Retired breeder mice are also useful for antibody production, aging studies or cancer research. However, it must be noted that the endocrinological status of the retired breeder is different from that of the group-housed virgin mouse. The estrous cycle of group-housed female mice is suppressed unless they are deliberately exposed to male pheromones (1). Retired breeder female mice have experienced all phases of the reproductive cycle. Development of mammary tumors in C3H/HeJ or C3H/HeOuJ mice depends upon a vertically transmitted mammary tumor virus and the hormonal changes associated with several pregnancies and lactation. Virgin C3H mice develop tumors less frequently and at an older age than do breeder mice (2).

Retirement age for breeder mice

After their litters are weaned, breeder mice that have reached specified ages are removed from the breeding colonies at The Jackson Laboratory. These breeder mice are known as "retired breeders."  "Retirement" age is the age at which reproductive performance declines below acceptable levels. This age varies among inbred strains. Mice from inbred strains that develop tumors at an early age have relatively young retirement ages. For example, AKR/J mice are retired at 6 months of age because many of these mice develop lymphocytic leukemia by 8-9 months of age (3). MRL/MpJ-lpr mice retire at 4 months of age because these mice develop massive lymph node enlargement. The lymphoproliferative disease that is characteristic of these mice begins around 8 weeks of age and by 4 months of age interferes with the well-being of the mouse. Most MRL/MpJ-lpr mice die between 17 and 22 weeks of age (4).

Mice from other frequently used inbred strains, e.g., C3H/HeJ, C57BL/6J, BALB/cJ, CBA/J, DBA/2J, A/J, retire from breeding colonies at 7 or 8 months of age. Inbred mice from one strain that are mated to inbred mice of a second inbred strain tend to have a longer period of efficient reproductive performance than inbred mice mated to other mice of the same strain. Mice used in hybrid matings retire between 8 and 11 months of age.

Physical appearance of retired breeder mouse models

Within a group of recently retired female breeder mice, some mice may be pregnant while other mice will be reproductively senescent. Still other mice in the group may be lactating or simultaneously pregnant and lactating. Retired breeder mice do not have the same physical appearance as young mice or age matched mice that have not been repeatedly bred. Female retired breeder mice from some inbred strains, e.g. BALB/cByJ and BALB/cJ, tend to be thin and have fur that is coarse and off white compared to that of younger virgin mice. Occasional female retired breeder mice from a variety of inbred strains will have thin fur or alopecia on the ventral abdomen. Retired breeder mice from C3H/HeJ and CBA/J strains tend to be fatter than retired breeders from other inbred strains of mice.

Retired male mice are aggressive

Retired breeder male mice have limited usefulness as research animals because they tend to be very aggressive toward other individuals. Male retired breeders from a few strains, e.g., C57BL/6J, can be shipped together in groups of five. However, even these male retired breeder mice may fight during transit. Upon arrival in a research facility, it is recommended that even the minimally aggressive retired breeder male mice be individually housed. Male retired breeders from SJL/J and BALB/cJ inbred strains are very aggressive. Male retired breeders from these two strains are not available unless the recipient is willing to accept the additional costs associated with shipping one mouse per compartment.

References

1. Whittingham DG and Wood MJ. 1983. Reproductive physiology. In: Mouse in Biomedical Research Volume 3. Foster HL. Small JD and Fox JG (eds). Academic Press. New York. pg 156-157.

2. Altman PL and Katz DD (eds). 1979. Inbred and genetically defined strains of laboratory animals. Part 1. Federation of American Societies for Experimental Biology. Bethesda, Maryland. pg 23.

3. Altman PL and Katz DD (eds). 1979. Inbred and genetically defined strains of laboratory animals. Part 1. Federation of American Societies for Experimental Biology. Bethesda, Maryland. pg. 45.

4. Staats J. 1985. Standardized nomenclature for inbred strains of mice: Eighth listing. Cancer Research 45:945-977.