Experiments With Skin Transplantation, Runt Disease, and Parabiosis in a New Inbred Rat Strain

Abstract

Bailey (1960), using the Holtzman albino rat, found that large homografts survived longer than small area grafts and concluded that his findings were comparable with those of Zotikov and Budik (1960). Matter and Chambler (1962), however, employing the same strain of Holtzman rat in their experiments, achieved equal survival times (100 days) in both large and small skin transplants and concluded that a state of histocompatibility must therefore exist. Since there are only a few inbred strains reported, other than in mice, an exact study of the degree of inbreeding in the Holtzman strain was therefore initiated.The Holtzman rat, commonly used in research, has been bred in a closed random system for 16 years. Five years ago the Holtzman Co. in Madison, Wis., opened a subsidiary firm in Houston, Texas. Since then the Houston branch has maintained a completely separate stock and has also used random selection for breeding purposes.A strain of rats with a high degree of genetic similarity can be obtained after 20 consecutive generations of brother-sister mating (Billingham and Silver, 1959). The Holtzman rat has been bred in a closed random system, and many more generations were necessary to reach a state of isogenicity.Therefore, skin transplantation, runt disease, and parabiosis were used as biological indicators in assessing the degree of histocompatibility.As yet, a reliable genetic test is not available to prove uniformity. Experiment 1. Skin TransplantationHoltzman rats weighing approximately 200 gm. were employed as indicated below. Homografts with an area of 40 sq. cm. were applied to the back of the host as described previously (Matter and Chambler, 1962). The red Oklahoma King rat was used for control experiments. Sex difference was observed throughout the experiments to avoid graft exchange between identical littermates.Houston rats. This set of 49 rats was divided into a set of 28 with male hosts and female donors and a set of 21 with female hosts and male donors. Forty-seven transplants survived 60 days. At that time 21 rats were used for further experiments. The remaining 26 carried their graft for more than 100 days (FIGURE 1A).One rat died 12 days after grafting with an intact donor skin and could not be followed. Another female host rejected its male donor skin after 44 days. I t was felt that this single failure was not significant enough, however, to in.. dicate a sex-linked incompatibility as described in other inbred strains of mice and rats (Eichwald and Silmser, 1955). 611