Influence of genetic background and age on the expression of the obese hyperglycaemic syndrome in Aston ob/ob mice.

Expression of the obese hyperglycaemic (bo/ob) syndrome in mice is modified by the background genome. The Aston colony carries the ob gene on a mixed background which produces a unique combination of different features shown by ob/ob mice on other backgrounds. The maximum body weight of Aston ob/ob mice exceeded that of other colonies, possibly reflecting a trait for higher growth rate in the background genome. The hyperphagia, marked hyperinsulinaemia and moderate hyperglycaemia observed during the development of the syndrome receded in old mice. Plasma glucagon concentrations in the fed state were similar to +/+ mice and did nor Vary throughout life. Hyperplasia of the B-cells increased inordinately during the development of the syndrome, but declined in older mice coincident with progressive intercellular vacuolation and the appearance of acinar-like cells within the islets. A-cell hyperplasia was greater in young mice, and A-cells became relocated throughout the islets of older mice. The distinct pattern of age-related changes in ob/ob mice indicates that experiments using this gene type should define clearly their age as well as genetic background.