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Immunology Today, vol. 6, No. 4, 1985

Kl(....r, Life span of mice

MRL/lpr/lpr

SIR, W e (Ref. 1 and unpublished observations) and others 2 5 have demonstrated that the life span and disease of autoimmunity-prone mice are modulated by the type and amount of fat present in their diet. However, in the course of our studies on the effects of fat in isocaloric diets on the immunopathology of M R L / l p r / l p r (MRL/1) mice (unpublished observation), we have been intrigued by the longer-than-reported survival of t h e ' reference' animals. This group was fed a normal rodent pellet diet (Ralston Purina, St. Louis, Missouri, chow no. 5001) which contains 4.5% rendered fat. W e observed that 55% of females and 65 % of males on this diet were still surviving at 12 months of age. Only 25% of mice maintained on a diet containing 9 % fat survived at 12 months of age. Similarly, a recent study by K u b o et al. 6 showed that male MRL/1 mice fed a high calorie diet (dying sooner than other diet groups) experienced 50% survival at 7 months of age and 90% mortality at 11 months. Yet according to the original observations by M u r p h y et al. 7 and Andrews et aL 8, male and female M R L / I have, respectively, a m e a n survival (50% mortality) of 5 and 5.5 months and 90 % of them are expected to

*** This letter was shown to D r Theofilopoulos, who replied as follows: SIR, H o m s y et al. suggest that variations in survival rates of M R L - l p r / l p r mice might be caused by the content o f fat in their regular diet. They indicate that, in the original description of M u r p h y and Roths ~and Andrews et al. 2, the reported 50% mortality at 5 and 5.5 months for female and male M R L - l p r / l p r mice, respectively, perhaps reflected a diet relatively rich in fat (6-10%). In their laboratory, where a diet of 4.5 % fat was used, 55 % o f females and 65 % o f males were alive by 12 months of age. In reviewing the diets used in our breeding • colony, we did not observe any changes in the originally reported survival rates of these mice, even when the diets had a fat content as low as 4 % . O u r observations span a six-year period. Therefore,

die at 7.3 and 8.6 months of age, respectively. Investigators from several other independent laboratories have mentioned to us that they have noted a similar p h e n o m e n o n with MRL/1 mice. These discrepancies led us to examine the composition of the diets used in the first studies of the MRL/1 strain. W e found that these diets contained between 6 % and 10 % fat 7.8; this level is 50 % to 110 % higher than the content of most regular rodent chows (4.5 %). Moreover, in our studies, diets containing 9 % fat greatly enhance the severity and accelerate the onset of disease in both N Z B / W 1 and M R L / I mice (unpublished observation). Therefore, the high fat diets used in these early observations on MRL/1 mice may well have influenced their survival pattern. T h e MRL/1 mouse is shortlived because it has a very active form of i m m u n e pathology. Thus this strain may reflect more acutely the effects of diet on i m m u n e function. Other factors might also account for or contribute to some of these discrepancies. For instance genetic drift or a generalized infection by Sendal virus, an agent known to cause immunosuppression 9, could influence results in certain mouse colonies. Nevertheless, investigators studying MRL/1 mice should be aware o f the dietary bias that characterizes the early studies of the pathology of this strain. Although the value o f these comparative analyses per se is not in question, the time course data obtained should not be used as a standard

although the diets might have effects on survival of lupus mice, as demonstrated by several investigators 3-~, the classically described survival rates do not appear to be affected by small variations in the percentage of fat included in their regular diet. A n alternative explanation for longer survival of certain M R L colonies, as n o t e d - b y both ourselves and M u r p h y (personal communication), might be related to the breeding practices whereby healthier breeders are selected over a period o f time, thereby extending the longevity of their offspring.

ARGYRIOS N. THEOFILOPOULOS Department of Immunopathology, Scripps Clinic and Research Foundation, La Jolla, CA 92037, USA.

reference, in view of the effects that high fat diets can exert on the disease of these animals. A similar effect of diet should also be considered with other mouse strains in which i m m u n e function is being measured. ~[~

j. HOMSY W. J. w. MORROW J. A. LEVY Cancer Research Institute, School of Medicine, University of California, San Francisco, CA 94143, USA.

References 1 Levy,J. A., Ibrahim, A. B., Shirai, T., a al. (1982) Proc. Natl Acad. Sd. USA 79, 1974-1978 2 Fernandes, G., Yunis, E.J., Smith, J. and Good, R. A. (1972)Proc. Soc. Exp. BiolMed. 139, 1189-1196 3 Fernandes, G., Yunis, E.J.,Jose, D. G. and Good, R. A. (1973) Int. Arch. Allergy 44, 770-782 4 Kelly, V. E. and Izui, S. (1983) Am. J. PathoL I I I, 288-297 5 Fernandes, G., Alonso, R. A., Tanaka, T., Thaler, H. T., Yunis, E.J. and Good, R. A. (1983) Proc. Natl Avad. Sci. USA 80, 874-877 6 Kubo, C., Noorbibi, K. D. and Good, R. A. (1984) Proc. Natl Acad. Sci. USA 81, 5831-5835 7 Murphy, E. D. and Roths, J. B. (1978) in Genetic Control of Autoimmune Disease (Rose, N. R., Bigazzi, P. E. and Warner, N. L., eds) pp. 207-220, Elsevier, Amsterdam 8 Andrews, B. S., Eisenberg R. A., Theofilopoulos A. N., et aL (1978).]: Exp. Med. 148, 1198-1215 9 Kay, M. M. B. (1978) Proc. Soy. Exp. Biol. Med. 158, 326

References 1 Murphy, E. D. and Roths, J. B. (1979) in Genetic Control of Autoimmune Disease (Rose, N. R., Bigazzi, P. E., and Warner, N. L. eds) pp 207-220, Elsevier, Amsterdam 2 Andrews, B. S., Eisenberg, R. S., Theofflopoulos, A. N., Izui, S., Wilson, C. B., MeConahey, P. J., Murphy, E. D., Roths, J. B. and Dixon, F. J. (1978)j. Exp. Med. 148, 1198-1215 3 Kubo, C., Day, D. K. and Good, R. A. (1984) Proc. Natl Aend. Sci. USA 8l, 5831-5835 4 Fernandes, G. and Good, R. A. (1984) Proc. Natl Acad. Sc£ USA 81, 6144-6148 5 Fernandes, G., Friend, P., Yunis, E.J. and Good, R. A. (1978) Proc. Natl Acad. Sci. USA 75, 1500-1504 6 Hurd, E. R.,Johnston, J. M., Okita, J. R., MacDonald, P. C., Ziff, M. and Gilliam, J. N. (1981)J. Ctin. Invest. 67, 476-485 7 Priekett, J. D., Robinson, D. R. and Steinberg, A. D. (1981)J. Clin. Invest. 68, 556-559 8 Levy, J. A., Ibrahim, A. B., Shirai, T., Ohta, K., Nagasawa, R., Yoshida, H., Estes, J. and Gardner, M. (1982) Proc. Natl Acad. Sci. USA 79, 1974-1978