Ku80 maintains the genome by repairing DNA doublestrand breaks (DSBs) through nonhomologous end joining (NHEJ), a pathway that repairs nonspecific DSBs and Rag-1 Rag-2 (Rag)-specific DSBs. As a result, Ku80 deletion results in phenotypes characteristic of defective repair for both nonspecific DSBs (c-radiation hypersensitivity and genomic instability) and Rag-specific DSBs (immunodeficiency). ku80 À/À mice also exhibit neuronal apoptosis, but we do not know the type of DSBs responsible for this response. In spite of genomic instability and immunodeficiency, cancer incidence is not increased in ku80 À/À mice. However, deletion of the tumor suppressor, p53 greatly increases pro-B-cell lymphoma in ku80 À/À mice due to IgH/c-Myc translocations suggesting that responses to Rag-specific DNA DSBs suppress cancer. Like suppression of pro-B-cell lymphoma, neuronal apoptosis requires p53 presenting the intriguing possibility that Rag-specific DSBs mediate neuronal development as they do lymphocyte development. Here we delete Rag-1 from ku80À/À mice to differentiate the impact nonspecific vs Rag-specific DSBs have on ku80 À/À mice. We find that deleting Rag-1 prevents pro-B cell lymphoma confirming Rag-induced DSBs induce this form of cancer. Both the triple mutant mice and the p53 À/À rag-1 À/À mice exhibit T-cell lymphoma and medulloblastoma; incidence of T-cell lymphoma is the same for both cohorts whereas incidence of medulloblastoma is higher for the triple-mutant cohort. Thus, p53-mediated neuronal apoptosis likely suppresses medulloblastoma in Ku80-deleted mice and Ku80 likely suppresses medulloblastoma by repairing nonspecific DNA DSBs instead of Rag-specific DSBs. Our observations are the first to show that Ku80 suppresses cancer caused by nonspecific DNA damage and we present a novel mouse model for medulloblastoma.

A 15-year-old Arabian mare from southern Louisiana with a 2-month history of periodic epistaxis and severe weight loss had a large, fibrosing, granulomatous mass containing numerous nodules ("kunkers") projecting dorsally into the nasopharynx, and was euthanized at the owner's request. In addition to these kunkers, the mass contained a single trematode tentatively identified as Fasciola hepatica. Several kunkers were removed, washed thoroughly in sterile water and embedded in nutrient agars; the fungus that grew out of them was identified as Conidiobolus lamprauges Drechsler (Entomophthorales: Ancylistaceae). This is the first report of C. lamprauges from any vertebrate mycosis, and only the third Conidiobolus species reported from vertebrates. Unlike many other entomophthoraleans, the fungus isolated from this mycosis grew well at 37°C. The possible means by which Conidiobolus species may infect vertebrates is discussed. These mycoses probably result most often from chronic exposure during sleep to conidia discharged from fungal growth on decaying plant material in the bedding.

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To examine the effect of laser thermal injury on Langerhans cells (LC) within the epidermis, the dorsal skin of mice and hairless guinea pigs was exposed to varying levels of laser irradiation using a thulium laser at a wavelength of 2.0 μm. At 6, 24 and 48 h post irradiation, animals were euthanized, skin samples prepared for histology and the epidermis obtained and stained by major histocompatibility complex-II staining (mice) or ATPase assay (hairless guinea pigs) for the enumeration of LC. Mouse skin exhibited histological evidence of thermal damage at 24 h post irradiation at even the lowest dose (0.14 W) and decreases in the numbers of epidermal LC were observed at all doses and decreases were proportional to dose. In contrast, hairless guinea pig skin only showed consistent histological evidence of thermal damage at the highest dose of irradiation (0.70 W) at 24 and 48 h post irradiation and exhibited a statistically significant decrease in numbers of epidermal LC only at this dose. Thus, epidermal LC depletion occurred in the skin of both mice and hairless guinea pigs in response to laser treatment and the magnitude of depletion directly correlated with the extent of thermal damage both within and between species.