logical appearance of tissue lesions, and nucleic acid or protein content of tissue. The requirement for any nutrient may vary with the criteria used. Traditionally, rapid growth leading to maximum body size at maturity has been the basis for measuring dietary adequacy on the assumption that a diet promoting maximum growth would be adequate for reproduction, lactation, and maintenance. Data have been published that test the validity of this assumption for the mouse. Knapka et al. (1977) found that diets producing maximum postweaning growth did not support maximum rates of reproduction. Since the mouse achieves one-third of its total growth during the suckling period, lactation imposes a heavier nutritional burden on the dam; this may influence some nutrient requirements more than others. Dubos et al. (1968) reported that a casein-starch diet that contained 0.05 percent magnesium was adequate for growth of mice, but sudden death occurred in some lactating females when they consumed that diet. An additional 0.02 percent magnesium prevented this syndrome, indicating the need for an increase in the magnesium requirement during lactation.

These results suggest that diets which support maximal growth are not optimal for reproduction. Therefore, for the mouse diet, the meaning of the term "adequate" may need to be expanded to indicate a range of nutrient intakes between minimal and harmfully excessive; the range will

vary at different stages of the life cycle. Nutrition investigators generally focus on nutrient requirements as minimal dietary concentrations. For life-span studies with mice, however, optimum dietary concentrations of energy and nutrients may have to be established. Although many studies have been conducted on the effects of diet on longevity, there are insufficient published data to estimate the nutrient requirements for long-term maintenance of mice.

Mice maintained in germ-free, gnotobiotic, or specific-pathogen-free environments, where the kinds and number of intestinal microorganisms are altered, may require different dietary concentrations of nutrients. Luckey et al. (1974) fed mice a sterilized diet, marginal in several vitamins, and observed decreased reproduction in germ-free as compared to conventionally reared mice. Allen et al. (1991) reported that adding 20 mg menadione sodium bisulfite/kg diet to the diets of hysterectomy-derived mice maintained in a specific-pathogen-free environment arrested a spontaneous outbreak of hemothorax.

Considering the many genetic and environmental factors that influence the nutrient requirements of laboratory mice, too few controlled studies have been conducted, particularly in recent years, to identify the nutrient requirements of this species. As a result the estimates of nutrient requirements are based on

• data accumulated many years ago involving mouse strains fed dietary ingredients that are no longer available or cannot be identified,

• experimental results derived from studies that were not designed to establish nutrient requirements,

• nutrient consumption by mice fed diets producing "acceptable performance," and

• the assumption that mouse nutrient requirements are similar to those of the rat.