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Animal research regulatory agencies have issued updated requirements for emergency response planning by regulated research institutions. A thorough emergency response plan is an essential component of an institution's animal care and use program, but developing an effective plan can be a daunting task. The author provides basic information drawn from the field of emergency management about best practices for developing emergency response plans. Planners should use the basic principles of emergency management to develop a common-sense approach to managing emergencies in their facilities.

We measured daily intracage ammonia levels and performed weekly assessments of CD1 male, female, and breeder mice housed within disposable, ventilated cages that remained unchanged for 28 d. We tested housing groups comprising 1, 3, or 5 sex-matched mice per cage and breeder pairs with litters. Mice housed in cages with higher concentrations of ammonia developed degeneration and inflammatory lesions in the nasal passages. Mean ammonia exposure levels that caused rhinitis were 181 ppm for 18 d. Ammonia exposures of 93 ppm for 16 d caused necrosis of the olfactory epithelium, whereas 52 ppm for 13 d caused epithelial degeneration. Observers could not detect visible signs of rhinitis or identify cages with elevated ammonia levels, nor did they identify any sick or distressed mice. Observers consistently assigned poorer welfare scores as cages became dirtier. We conclude that we can extend the cage-change interval to at least 28 d for disposable, ventilated caging housing a single CD1 mouse. Cages containing 3 CD1 mice of either sex should be changed biweekly, and cages containing 5 CD1 mice or breeder pairs should be changed at least once weekly.

Earthquakes can occur in most regions of the United States, so it might be necessary to reinforce vulnerable animal facilities to better protect research animals during these unpredictable events. A risk analysis should include an evaluation of the seismic hazard risk at the proposed building site balanced against the estimated consequences of losses. Risk analysis can help in better justifying and recommending to building owners the costs of incorporating additional seismic reinforcements. The planning team needs to specify the level of post-earthquake building function that is desired in the facility, and then design the facility to it.

Research animals need protection from the catastrophic losses that can occur during disasters. The best method of protecting animals is to house them in facilities that have been reinforced using disaster-resistant construction methods. The authors explain the use of site-specific risk analysis to determine the proper building site and features.

Research facilities have an obligation to provide appropriate care for animals used in studies, even in the event of a disaster or emergency situation. Each facility should develop a planned response for emergency situations that affect their research animals. Appropriate resources and personnel should be identified during development of emergency management plans.

Autoimmune MRL/lpr mice were treated for 12-14 weeks with anti-CD4 monoclonal antibody to define the role of CD4+ T cells in the pathogenesis of the inflammatory central nervous system (CNS) lesions, arthritis and sialadenitis characteristic of the strain. Anti-CD4 therapy effectively prevented the development of CNS lesions and arthropathic changes. Marked depletion of CD4+ T cells was documented in the mononuclear cells infiltrating the major salivary glands but the severity of sialadenitis was significantly increased by chronic anti-CD4 immunotherapy. This dissociation between beneficial and harmful effects of anti-CD4 treatment in the MRL/lpr mouse suggests that the net regulatory effect of CD4+ T cells on the underlying autoimmune-mediated inflammatory process may be positive or negative depending on the organ system involved. The pathogenetic mechanisms of inflammation and tissue destruction in this model of systemic autoimmune disease are in some instances target organ-specific.

Objective: To determine if neurologic impairment is related to progressive autoimmune disease in 3 murine models of systemic lupus erythematosus (SLE): MRL/lpr, NZB, and NZB/WF1., Methods: Sensorimotor function, learning, and memory were tested within strains at specific ages, before and after the appearance of SLE. These parameters were also compared between strains for young and older lupus mice and their congenic controls with reduced autoimmune disease (MRL/lpr versus MRL/+; NZB versus NZB/xid)., Results: Abnormal neurologic features were present at a much higher frequency in MRL/lpr mice than in age-matched MRL/+ control mice, and sensorimotor function deficits were also seen in NZB/WF1 mice. Strains that develop lupus showed deficits on a water-escape, distal cue discrimination task and on a food-rewarded, proximal cue discrimination task, but the cognitive impairments were not global., Conclusion: MRL/lpr, NZB, and NZB/WF1 mice differed in terms of which behaviors were impaired as well as when those impairments appeared.

The pathologic phenotype of the testis in both prepuberal and postpuberal male weaver mutant mice was studied by light microscopy. Morphometric analysis of seminiferous tubules was carried out. Epididymal fluid was examined for the presence of spermatozoa. The seminiferous tubules of 21-day-old prepuberal weaver mutant mice lacked patent lumina and had more degenerated cells than control mice. Fifty-six day-old weaver mutants had many germinal epithelial cells located within the adluminal compartment that were in advanced stages of degeneration. Round spermatids were enlarged and multinucleated. Round spermatids and spermatocytes had sloughed into the lumen. Compared to control mice, elongated spermatids were seen less frequently. In older weaver mice, the degenerative process involved germ cells in both the adluminal and basal compartments. In 143- and 226- day-old weaver mutants, the Sertoli cells were atrophic. Diameters of seminiferous tubules in weaver mice were significantly reduced when compared to control mice. Sperm were either absent or very low in number in the epididymal fluid of postpuberal weaver mice. We conclude that spermatogenesis is abnormal in male weaver mutant mice. The testicular phenotype is characterized by a degenerative process that affects both germ cells and supporting cells.

This is the initial report of an unusually high incidence of exencephaly in inbred New Zealand White (NZW) mice and the congenic NZW-xid strain, in which animals are homozygous for the recessive X-linked immune deficiency (xid) gene. The predominant expression of exencephaly in female pups and a disproportionate decrease in numbers of female pups in litters suggested that exencephaly was part of a continuum of lethal defects expressed preferentially in females. Genetic influence in the expression of exencephaly in NZW mice was postulated because environmental cohort controls did not express this defect. NZW mice are an additional model for studying the pathogenesis of neural tube defects.

The brains of pathogen-free autoimmune MRL/lpr, NZBWF1 and NZB mice were examined for central nervous system (CNS) inflammation in premoribund 8-week-old animals and at ages when active systemic lupus erythematosus (SLE) was present. CNS inflammation was observed only in MRL/lpr mice. Immunohistochemical studies of brains from young MRL/lpr mice found that infiltrates were composed primarily of CD4+ cells. Older MRL/lpr mice (22 and 26 weeks of age) had CD4+ cells predominantly, but CD8+ and B220+ cells were also present. Perivascular leakage of IgG was a prominent and unexpected finding in the MRL/lpr model. Congenic MRL/+ mice with late-onset autoimmunity had no inflammatory cells in brain tissue, and there was no perivascular staining with IgG or albumin. Our findings suggest that MRL/lpr mice are a useful model for studies of lupus-associated CNS inflammatory disease, and perivascular leakage may be a primary mechanism for entry of IgG into the brain.

Phenol-extracted Escherichia coli endotoxin was infused into ligated jejunal loops in 3 pigs. Tissue samples were collected from the center of each loop 6 hours later and examined with scanning electron microscopy. Control loops infused with pyrogen-free water were examined, as well as nonligated biopsy and blind-loop samples. Loops infused with endotoxin had predominantly ridge-shaped villi, many actively secreting goblet cells, and numerous large epithelial ulcerations involving the tips and sides of villi. Tight junction disruption between epithelial cells was observed in 1 pig. In contrast, small ulcers were rarely seen in ligated control loops. Villi were predominantly tongue-shaped, and goblet cell activity was moderate. Pathologic changes were greater in endotoxin-infused loops than in water-infused loops at 6 hours after infusion.

Effects of UV radiation and irradiation followed by challenge exposure with Moraxella bovis on the corneal epithelium were studied in 6 calves by scanning electron microscopy. After UV irradiation, the number of dark cells comprising the surface epithelium increased. Many epithelial cells were in various states of degeneration and were characterized initially by large round nuclei, whereas sloughing and peeling were characteristic of the last degenerative stage. All M bovis-infected irradiated eyes had large numbers of degenerating cells, deep epithelial defects, fibrin strands, surface inflammatory cells, and debris. A few M bovis organisms were randomly attached to the cornea before visible ulceration. There were many inflammatory cells between the ulcerated corneal epithelium and adjacent nonulcerated epithelium. Epithelial cells at the margin of the ulcer appeared swollen. Light, dark, and intermediate epithelial cell types could not be distinguished peripheral to the ulcer.