Exocrine pancreatic insufficiency syndrome in CBA/J mice. Ultrastructural study.

The pathogenesis of a spontaneously occurring exocrine pancreatic insufficiency (EPI) syndrome in CBA/J mice was studied at the ultrastructural level. Initial cytologic manifestations of this syndrome are seen as a progressive digestion of the zymogen granules, beginning at the periphery and proceeding toward the granule interior. Granule membrane breakdown, fusion of neighboring granules, and a release of zymogen contents into the cytoplasm are frequently observed in later stages; in some cases the entire granule contents appear digested before membrane breakdown is observed. In either case, pathologic changes are subsequently observed in mitochondria and rough endoplasmic reticulum. Remnants of lysed cells are then engulfed by invading macrophages, and infiltration by fat cells is observed. Secretory ducts and islets of Langerhans show no pathologic changes even after total autolysis of the exocrine pancreas. Morphologic evidence showing zymogen granule destabilization, coupled with biochemical evidence presented in an accompanying paper, indicate that intracellular autodigestion is the mechanism of exocrine cell death.     

Deleterious effects of irradiation and bone marrow transplantation therapy in the genetically anemic an/an mouse

The efficacy and outcome of bone marrow transplantation therapy following lethal irradiation were examined in syngeneic mice that had a hereditary macrocytic anemia (an/an) or were genotypically normal (+/+). Successful RBC and WBC replacement, based on blood cell parameters and donor genetic markers, were observed in all combinations of transplant therapy. Nevertheless, the an/an mice died prematurely several months after treatment, whether they received +/+ or an/an marrow cells. In contrast, the +/+ recipients of either +/+ or an/an marrow cells survived for at least 1 year after transplantation. Premature death of the an/an mice was associated with lymphopenia, anemia, kidney lesions, and severe pathogen-free pneumonitis. On the basis of our results, we hypothesize that the premature deaths of an/an mice are caused by a kind of chronic irradiation damage to which an/an mice are especially susceptible.     

Society for Reproductive Biology Founders' Lecture 2005. Control of metabolic cooperativity between oocytes and their companion granulosa cells by mouse oocytes

Oocytes orchestrate the rate of follicular development and expression of genes in the surrounding granulosa cells. Oocytes are deficient in their ability to carry out some metabolic processes, such as glycolysis and amino acid uptake, and depend on the cooperation of granulosa cells to carry out these processes. In this dependency, the oocyte was previously considered a passive recipient of the nutritional support from granulosa cells. However, recent studies indicate an active role for the oocyte in controlling metabolic activity in granulosa cells. The ability of oocytes to control granulosa cell metabolism is achieved, at least in part, by regulating granulosa cell expression of genes encoding proteins involved in the metabolic processes. This review summarises current knowledge of intercellular communication between oocytes and granulosa cells from the perspective of oocyte control of gene expression in granulosa cells and metabolic cooperativity between the two cell types. The oocyte probably controls metabolism in granulosa cells to provide metabolites for its own development. In addition, we hypothesise that oocytes use their ability to regulate metabolic pathways in granulosa cells to orchestrate the rate of follicular development.