Two inbred strains of CBA mice have been bred and studied for 15 years in our laboratory. Both were given to us by Dr. L.C. Strong -- the first, CBA/Ki, to Dr. Kirschbaum in 1941, and the second, CBA/St/Ki, to me in 1963. They have been inbred, brother-sister, for approximately 80 and 53 generations, respectively, since 1952 and 1963. During this time, the geographic location of the Ki colony has changed as my husband and I have moved: 1952-1954 at the University of Illinois College of Medicine, Chicago; 1954-1971 at Baylor College of Medicine in Houston; 1971-1974 at the Medical College of Georgia in Augusta; 1974 to the present at Northeastern Ohio Universities College of Medicine (temporarily housed at Akron General Medical Center) 1978- now located permanently in Rootstown, Ohio.
The external appearance of mice of the two strains is similar, but the strains differ in many ways.
1. Histocompatibility. Within each strain normal skin autografts and isografts were uniformly successful, while allografts between the strains were always sloughed between two and four weeks (up to 200 mice). Tumor transplants of several different types likewise were successful within each strain, but only rarely crossed strain barriers ( 1). That is, of seven CBA/St Ki tumors, none grew in CBA/Ki. Of 13 CBA/Ki tumors, many of which had been transplanted numerous generations, only two tumor lines had progressive growths in CBA/St/Ki [4/20 mice of 2663 stomach carcinoma line from T-75 on, and 21/21 in 2468 uterine tumor line from T-285 on (approximately 300 mice used)] ( 1). In addition, the CBA/Ki tumor 2663 is in the T-360 transfer now, still transplants successfully in the strain of origin, and maintains its lipid-mobilizing characteristics which result in the anorexia, cachexia, and death of the animals with only a relatively small subcutaneous transplant ( 2).
2. Spontaneous tumors. Occurrence of three types of tumors has been examined. Tumors of the reticular system, primarily systemic leukemia, occur in low incidence in both strains and both sexes (male= M, female = F): CBA/Ki- F=3.1% (27/871) at 578 days (194-780), M=1.8% (14/766) at 554 days (210-743); CBA/St/Ki - F=5.7% (15/261) at 627 days (456-992), M=4.0% (9/224) at 606 days. Hepatomas occurred more frequently in males than females of both strains: CBA/Ki - F=0.6% (5/871) at 607 days (481-796), M=8.4% (64/766) at 593 days (259-1016), CBA/St/Ki - f=0, M=8.0% (18/224) at 656 days. On the other hand, mammary cancer is rare in CBA/Ki, but occurs in CBA/St/Ki on the average of 50% ( 3). The incidence and age of death in females were: Texas 39% (43/111) at 479 days (189-957); Georgia 48% (43/90) at 457 days (242-700); and 44% (35/80) at Ohio - 367 days (221-584) (still in progress). The incidence in CBA/St/Ki virgin females is: Georgia - 27% (18/66) at 598 days (460-729); Ohio - in progress - so far approximately 20%.
3. Goldthioglucose-induced obesity varies between the two strains. A series of doses ranging from 0.2 to 1.5 mg/g body weight were tested by one injection i.p. to mice of both sexes at 2-3 months of age ( 5). Only CBA/Ki mice respond consistently, that is, a dose of 0.35 mg/g body weight results in no toxicity, no death, and 100% obesity. Associated with the obesity are a transitory increase in food consumption, hypothalmic lesions, and alterations in endocrine function. Mice of the CBA/St/Ki strain do not respond in the same manner, since many mice die or become ill following the injection or do not become obese at a given dose level.
4. Retinal degeneration (rodless retina). In mice of the CBA/Ki strain the retina at birth is indistinguishable from the retina of other strains including CBA/St/Ki. By 15 days the outer nuclear layer is reduced to a few nuclei in thickness; that is, there is a loss of the rod and outer molecular layers and a reduction of the external nuclear layer; by 35 days the retina lacks photoreceptors ( 6). Mice of CBA/St/Ki strain have an intact photoreceptor layer.
5. Feeding patterns. In CBA/Ki mice the feeding pattern is atypical with periodic dominance of food consumption in the period of 8 a.m. to 4 p.m. and is due to a circadian rhythm with a period of greater than 24 hours. On the other hand, mice of the CBA/St/Ki strain have a more typical feeding pattern with the constant dominance of food consumption between 4 p.m. and 8 a.m., that is, a nocturnal pattern ( 7, 8).
Since Strong first developed the CBA strain(s), numerous mouse colonies throughout the world have been breeding CBA mice, many of which have reported differences in mammary cancer incidence. We have reported our observations over a number of years on two CBA strains which differ in multiple characteristics, but which have remained stable.
1. Liebelt, A.G., and Liebelt, R.A. (1967). In Methods in Cancer Research, Vol. I, p. 143. Academic Press, New York.
2. Liebelt, R.A., Gehring, G., Delmonte, L., Shuster, G., and Liebelt, A.G. (1974). Ann N.Y. Acad. Sci. 230: 547.
See also PubMed.
3. Liebelt, A.G., and Liebelt, R.A. (1967). In Carcinogenesis: A Broad Critique (University of Texas, M.D. Anderson Hospital), p. 315. Williams & Wilkins, Baltimore.
4. Dmochowski, L., Langford, P.L., Williams, W.C., Lieblet, A.G., and Liebelt, R.A. (1968). J. Natl. Cancer Inst. 40: 1339.
See also MGI.
5. Liebelt, R.A., Sekiba, K., Liebelt, A.G., and Perry, J.H. (1960). Proc. Soc. Exp. Biol. Med. 104: 689.
See also PubMed.
6. Caley, D.W., Johnson, C., and Liebelt, R.A. (1972). Am. J. Anat. 133: 179.
See also MGI.
7. Ishiki, D.M., (1968). Thesis of M.S., Baylor University College of Medicine, Houston, Texas.
8. Liebelt, R.A., Ishiki, D., and Liebelt, A.G. (1973). Fed. Proc. 32: 383.