Abstract.A life span study of 900 female virgin Han:NMRI mice (300 outbred controls, 300 of a fat subline, and 300 of a lean subline) was done to determine the occurrence of spontaneous disease with ad libitum or restricted feeding. Major nonneoplastic lesions in the glandular stomach were erosions, ulcers and adenomatous hyperplasia of the fundus. Ulcers, ranging in incidence with ad libitum feeding from 5 to 9% and with food restriction from 13 to 34%, either occurred secondary to other diseases or were due to stress associated with food restriction, causing death mainly in the lean subline. Adenomatous hyperplasia was most common in the control group (4 l0/o); the frequency increased with age and was significantly reduced by food restriction. The etiology of adenomatous gastric hyperplasia is yet unknown. However, a lack of antiparietal cell antibodies, as determined by an immunofluorescent technique, indicates that an autoimmune disorder is not involved and an increase in antral gastrin cells, as determined by avidin-biotin peroxidase immunocytochemistry, suggests a hormonal involvement in pathogenesis.Neoplastic and selected nonneoplastic lesions have been reported on a life span study of food restriction of outbred Han:NMRI mice and two sub line^.^^-^^ Nonneoplastic lesions of the stomach were mainly ulcers of the glandular portion partly due to food r e~t r i c t i o n '~.~~~~~ or in association with physical stress similar to acute stress ulcers in humans, e.g., during prolonged illness.3o Reports of spontaneous gastric ulcers in rats and mice are infrequent, and ulcers are often limited to the f o r e~t o r n a c h .~J~,~~ The predominant gastric lesion of Han:NMRI mice was, however, an adenomatous hyperplasia of the fundus. Of unknown origin, it is comparable to the lesion seen in I strain mice.32g41 Apart from assessment of incidence and influence of food restriction on gastric hyperplasia, the present investigation is concerned with a histomorphologic description of this lesion and with immunohistologic studies that were carried out to discern possible autoimmunez4 and hormonal*J 1~1 2 , 4 4 influences on development.
Materials and MethodsA life span study on spontaneous mortality and diseases was camed out on a total of 900 female virgin Han:NMRI mice that were composed of three groups: 300 mice of a fat subline (originally selected for a high body weight at an age of 4 weeks), 300 mice of a lean subline (selected for low body fat content of the parents), and 300 outbred control animals (nonselected). The sublines (1 2th and 13th generation of selection) and controls were obtained from a selection experiment from the Department of Population Genetics and Data Processing of the Central Institute for Laboratory Animal Breeding (Annual Reports of the Central Institute for Laboratory Animals 1975-1 980, Hermann-Ehlers-AIlee 57, D-3000 Hannover, FRG). Animals entered the experiment at an age of 8 weeks. They were kept in one room of a bamertype animal house with 22 & 1 C room temperature, 55 i 5% relativ...