RESUMO
Most academic research colonies of mice are endemically infected with enterohepatic Helicobacter spp. (EHS). We evaluated EHS prevalence in surveillance mice before and after a 10-y period of requiring that imported mice be free of EHS by embryo transfer rederivation or purchase from approved vendors. In 2009, composite fecal samples from CD1 surveillance mice representing colony health in 57 rooms located in 6 facilities were evaluated for EHS infection by using PCR assays. Fecal samples were screened with primers designed to detect all known EHS, and positive samples were further assayed by using primers specific for H. hepaticus, H. bilis, H. rodentium, and H. typhlonicus. Most EHS were detected in surveillance mice within the first month of dirty bedding exposure, with prevalence ranging from 0% to 64% as monoinfections or, more commonly, infections with multiple EHS. Compared with 1999 prevalence data, EHS remained endemic in colonies importing the lowest number of EHS-free mice. EHS were absent or the prevalence was greatly reduced in colonies receiving the highest percentage of EHS-free mice. This study demonstrates that the management decision to require exclusive importation of EHS-free mice reduced EHS prevalence on an institutional scale without intensive labor and expense associated with other techniques or interference with research objectives.
Assuntos
Animais de Laboratório/microbiologia , Infecções por Helicobacter/veterinária , Doenças dos Roedores/epidemiologia , Doenças dos Roedores/microbiologia , Organismos Livres de Patógenos Específicos , Criação de Animais Domésticos/métodos , Animais , Roupas de Cama, Mesa e Banho/microbiologia , Roupas de Cama, Mesa e Banho/veterinária , DNA Bacteriano/análise , Transferência Embrionária , Fezes/química , Fezes/microbiologia , Helicobacter/genética , Helicobacter/isolamento & purificação , Infecções por Helicobacter/epidemiologia , Infecções por Helicobacter/prevenção & controle , Abrigo para Animais , Camundongos , Reação em Cadeia da Polimerase , Pesquisa , Doenças dos Roedores/prevenção & controleRESUMO
Microbiologic surveillance is essential for murine health maintenance. At our institution, female progeny of inhouse-bred CD1 mice are used in both the transgenic facility and health-surveillance program. To reduce overall animal use, the male progeny, otherwise slated for euthanasia due to a lack of utility, also were enrolled as sentinels. However, veterinary technicians noted excessive fighting among cohoused male surveillance mice that was not resolved by environmental enrichment. After review of factors known to influence aggression in male mice, early castration was selected as the most likely approach to eliminate aggressive behavior among cohoused male mice. Male mice were castrated before 1 mo of age and then placed into the surveillance program. Each week, veterinary technicians recorded all incidences of fighting in cages of castrated and noncastrated male surveillance mice to determine differences between groups. Over a 3-mo period, the overall prevalence of fighting in cages of intact male mice was 64% (14 of 22 cages); although all intact male mice were used preferentially for complete necropsy surveillance time points, one of these cages required separation and 4 cages housed mice that incurred severe fight wounds requiring both separation and euthanasia. In comparison, a 0% (0 of 16 cages) prevalence of fighting was observed among castrated male mice. Castration eradicated pain and distress associated with fighting, thereby constituting a refinement, and allowed the use of male mice from the breeding colony for surveillance, thereby reducing the total number of mice bred for surveillance. In conclusion, castration is a minimally invasive, safe, humane, rapid method to eliminate conspecific aggression among male CD1 surveillance mice.
Assuntos
Agressão , Comportamento Animal , Camundongos/fisiologia , Camundongos/cirurgia , Orquiectomia , Bem-Estar do Animal , Animais , Animais de Laboratório , Meio Ambiente , Feminino , Humanos , Masculino , Camundongos/psicologia , Prevalência , Organismos Livres de Patógenos EspecíficosRESUMO
Neoplastic epithelia may remain dormant and clinically unapparent in human patients for decades. Multiple risk factors including mutations in tumor cells or the stromal cells may affect the switch from dormancy to malignancy. Gene mutations, including p53 mutations, within the stroma of tumors are associated with a worse clinical prognosis; however, it is not known if these stromal mutations can promote tumors in genetically at-risk tissue. To address this question, Apc(Min/+) and Apc(Min/+) Rag2(-/-) mice, which have a predilection to mammary carcinoma (as well as wild-type (wt) mice), received mesenchymal stem cells (MSC) with mutant p53 (p53MSC) transferred via tail vein injection. In the wt mouse, p53MSC circulated in the periphery and homed to the marrow cavity where they could be recovered up to a year later without apparent effect on the health of the mouse. No mammary tumors were found. However, in mice carrying the Apc(Min/+) mutation, p53MSC homed to mammary tissue and significantly increased the incidence of mammary carcinoma. Tumor necrosis factor (TNF)-alpha-dependent factors elaborated from mesenchymal cells converted quiescent epithelia into clinically apparent disease. The increased cancer phenotype was completely preventable with neutralization of TNF-alpha or by transfer of CD4(+) regulatory T cells from immune competent donors, demonstrating that immune competency to regulate inflammation was sufficient to maintain neoplastic dormancy even in the presence of oncogenic epithelial and stromal mutations. The significant synergy between host immunity and mesenchymal cells identified here may restructure treatments to restore an anticancer microenvironment.