A retrospective review of postapproval monitoring at a large academic institution.

Institutional Animal Care and Use Committees (IACUCs) are federally mandated to ensure the welfare of animals used in research, testing and teaching. An IACUC must oversee institutional animal care and use programs and promote compliance with all regulations and policies. Postapproval monitoring (PAM) is one administrative tool that an IACUC can implement to help fulfill its federal and societal responsibility. Here, the authors describe the PAM program at a large academic institution, considering the program's accomplishments and how the program has changed since its inception. The authors also provide a retrospective analysis of compliance records during the first 10 y of the program, which demonstrate improved compliance following initiation of PAM.

Alopecia in IL-10-deficient mouse pups is c-kit-dependent and can be triggered by iron deficiency.

Hair loss (alopecia) can result from a variety of metabolic, endocrine, immunologic, and environmental causes. This investigation was undertaken to determine the mechanisms underlying the sporadic development of alopecia in litters from C57BL/6 interleukin-10-deficient (Il10(-/-)) mice. All pups in affected litters demonstrated alopecia by postnatal days 17-19, with hair loss from their trunks but not from their head, base of tail, or feet. Histopathology revealed distorted hair follicles containing broken hair shafts and prominent dermal infiltrates containing increased numbers of activated mast cells. Hair re-growth began soon after weaning, suggesting that the alopecia was triggered by factors transmitted during lactation. Milk from Il10(-/-) dams induced macrophage secretion of pro-inflammatory cytokines in vitro regardless of whether or not their pups developed alopecia. Feeding dams a diet containing 3-6 ppm iron increased the percentage of litters with alopecia to 100% for pups with mast cells, with 0% alopecia in mast cell-deficient pups. When dams were fed a diet containing 131 ppm iron, significantly lower haemoglobin and hematocrit values were observed in pups from litters with alopecia (71%; 5 of 7 litters) compared to litters without alopecia. Genetic or pharmacologic inhibition of c-kit that resulted in depletion of mast cells in pups prevented hair loss in at-risk litters. These studies demonstrate that maternal iron-restricted diets enhance the incidence of alopecia in IL-10-deficient mouse pups and suggest mast cells as potential effector cells. Further studies are indicated to further explore the mechanisms involved and to determine how mast cells may contribute to alopecia in humans.

Helicobacter infection decreases reproductive performance of IL10-deficient mice.

Infections with a variety of Helicobacter species have been documented in rodent research facilities, with variable effects on rodent health. Helicobacter typhlonius has been reported to cause enteric disease in immunodeficient and IL10(-/-) mice, whereas H. rodentium has only been reported to cause disease in immunodeficient mice coinfected with other Helicobacter species. The effect of Helicobacter infections on murine reproduction has not been well studied. The reproductive performance of C57BL/6 IL10(-/-) female mice intentionally infected with H. typhlonius, H. rodentium, or both was compared with that of age-matched uninfected controls or similarly infected mice that received antihelicobacter therapy. The presence of Helicobacter organisms in stool and relevant tissues was detected by PCR assays. Helicobacter infection of IL10(-/-) female mice markedly decreased pregnancy rates and pup survival. The number of pups surviving to weaning was greatest in noninfected mice and decreased for H. rodentium > H. typhlonius >> H. rodentium and H. typhlonius coinfected mice. Helicobacter organisms were detected by semiquantitative real-time PCR in the reproductive organs of a subset of infected mice. Treatment of infected mice with a 4-drug regimen consisting of amoxicillin, clarithromycin, metronidazole, and omeprazole increased pregnancy rates, and pup survival and dam fecundity improved. We conclude that infection with H. typhlonius, H. rodentium, or both decreased the reproductive performance of IL10(-/-) mice. In addition, antihelicobacter therapy improved fecundity and enhanced pup survival.

Helicobacter typhlonius and Helicobacter rodentium differentially affect the severity of colon inflammation and inflammation-associated neoplasia in IL10-deficient mice.

Infection with Helicobacter species is endemic in many animal facilities and may alter the penetrance of inflammatory bowel disease (IBD) phenotypes. However, little is known about the relative pathogenicity of H. typhlonius, H. rodentium, and combined infection in IBD models. We infected adult and neonatal IL10-/- mice with H. typhlonius, H. rodentium, or both bacteria. The severity of IBD and incidence of inflammation-associated colonic neoplasia were assessed in the presence and absence of antiHelicobacter therapy. Infected IL10-/- mice developed IBD with severity of noninfected (minimal to no inflammation) < H. rodentium < H. typhlonius