Neuroethology: a neuronal self-defense mechanism in fly larvae

The detection of harmful stimuli - nociception - has been suggested to rely on evolutionarily conserved neuronal mechanisms. A recent study has shown how the activity of nociceptive neurons in Drosophila larvae triggers a defense mechanism against a parasitoid wasp.     

广东省屏障设施小鼠群中小鼠肝炎病毒感染情况

目的了解我省屏障设施小鼠群中小鼠肝炎病毒（MHV）感染情况。方法收集2003-2007年实验动物小鼠血清样品的监测数据,并对MHV感染情况有关数据进行分析。结果在6个屏障设施内抽检小鼠,5个屏障设施内抽检的样品检出MHV毒抗体阳性,检出率分别为1.4%,2.4%,2.8%,2.6%,13.2%。品系方面主要分布在BALB/c,BALB/c-nu/nu,NIH三个品系,检出率分别为3.6%,14%,7.1%。结论屏障设施小鼠群中小鼠肝炎病毒感染较为普遍。     

Genetic Architecture of Skewed X Inactivation in the Laboratory Mouse

X chromosome inactivation (XCI) is the mammalian mechanism of dosage compensation that balances X-linked gene expression between the sexes. Early during female development, each cell of the embryo proper independently inactivates one of its two parental X-chromosomes. In mice, the choice of which X chromosome is inactivated is affected by the genotype of a cis-acting locus, the X-chromosome controlling element (Xce). Xce has been localized to a 1.9 Mb interval within the X-inactivation center (Xic), yet its molecular identity and mechanism of action remain unknown. We combined genotype and sequence data for mouse stocks with detailed phenotyping of ten inbred strains and with the development of a statistical model that incorporates phenotyping data from multiple sources to disentangle sources of XCI phenotypic variance in natural female populations on X inactivation. We have reduced the Xce candidate 10-fold to a 176 kb region located approximately 500 kb proximal to Xist. We propose that structural variation in this interval explains the presence of multiple functional Xce alleles in the genus Mus. We have identified a new allele, Xce^e present in Mus musculus and a possible sixth functional allele in Mus spicilegus. We have also confirmed a parent-of-origin effect on X inactivation choice and provide evidence that maternal inheritance magnifies the skewing associated with strong Xce alleles. Based on the phylogenetic analysis of 155 laboratory strains and wild mice we conclude that Xce^a is either a derived allele that arose concurrently with the domestication of fancy mice but prior the derivation of most classical inbred strains or a rare allele in the wild. Furthermore, we have found that despite the presence of multiple haplotypes in the wild Mus musculus domesticus has only one functional Xce allele, Xce^b. Lastly, we conclude that each mouse taxa examined has a different functional Xce allele.     

实验小鼠种群管理（英文）

2009年11月份在西安举行由中国实验动物学会发起的实验动物医药技术培训研讨会上,本人做了关于实验小鼠种群管理的演讲。其主题涵盖了小鼠繁殖性能的维护和基因工程种群的管理。本篇文章的目的在于强调其所涵盖的材料并为进一步研究提供参考。如若对本文所讨论的内容希望有更深刻的理解,这篇文章所引用的参考资料值得进一步的阅读。另外本文未涉及远交系小鼠的繁殖培育和基因管理,但如有需要可以联系本文作者,可推荐需阅读的材料清单。     

实验小鼠在癌症研究中的应用及其进展

小鼠是生物医学研究中使用数量最多的哺乳类实验动物。人类利用小鼠模型进行癌症研究已有100多年的历史,小鼠大量的遗传变异可作为研究人类癌症的借鉴。特别是近年来,培育成功的转基因、基因敲除等遗传工程小鼠模型,使我们对人类癌症发生有了深刻的认识,为评估癌症的诊断方法,革新预防和治疗方案提供了一个很有价值的平台。本文着重介绍了癌症研究中常用的小鼠模型、GEM模型及取得的最新进展等,分析了小鼠肿瘤模型的局限性,并对其发展趋势进行展望。     

实验动物的环境与福利

实验动物在生物科学研究领域中的应用不断发展,其饲养环境和福利保障的问题已越来越被国际所关注。实验动物的环境与福利不仅是对动物本身的保护,更重要的是对动物试验结果的保证。本文详细论述了大环境（温度、湿度、气流等方面）及小环境（笼具、饲养密度、垫料）对实验动物福利的影响,通过总结国内外的研究概况,旨为我国改善和提高实验动物的福利提出一些思路。     

实验用小型猪环境条件控制指标比较

本文比较了中国、美国、欧洲、加拿大等国家及两个主要生产和实验企业关于小型猪环境条件指标控制情况,提出我国实验用小型猪环境条件控制标准的建议。     

Possible Derivation of the Laboratory Mouse Genome from Multiple Wild MUS Species

Laboratory strains of mice are thought to be derived from wild populations of Mus domesticus. Many instances of non-domesticus genetic information fixed in these strains have been described, however, and the amount of strain-to-strain genetic variation exceeds that found in wild domesticus populations. In order to estimate the extent of the non-domesticus contribution to laboratory mouse genomes, and to determine whether it could account for observed variation, we have used computer simulations to investigate the properties of genetically marked chromosomal segments and the distribution of residual allogenicity at various times during inbreeding. A locus or chromosomal segment is allogenic if it is unfixed within a lineage at a given time. The odds of fixation of a foreign chromosome segment are predicted to be an exponentially decreasing function of its length. The median segment length is predicted to be 17 centimorgans. Available data for markers of chromosomes 1, 9 and 12 in recombinant inbred strain sets conform to these predictions. Together, the results suggest that introgression of non-domesticus chromosomes and segregation of residual allogenicity are sufficient to account for the genetic diversity observed among inbred mouse strains and substrains.     

我国实验小鼠群中巨细胞病毒自然感染情况的调查

迄今为止,有关MCMV在实验小鼠群中的自然感染情况报道极少。我们在MCMV实验感染的基础上对国内常用的小鼠品系进行MCMV自然感染的调查。结果发现在334份不同品系小鼠颌下腺中无1份分离出MCMV,而特异性抗体存在于所检查的10个品系中,阳性率为10.9—87.5％。抗体阳性率与鼠龄有关,随鼠龄的增长而上升。对全国部分省市40家实验动物机构的556份小鼠血清的调查结果表明MCMV的抗体阳性率达61.0％,提示在我国实验小鼠群中MCMV的自物感染是相当普遍的。这种病毒分离阴性而抗体阳性的状态表明隐性感染和潜伏感染是MCMV自然感染的主要方式。     

系统低温生物学技术在实验小鼠资源保存中的建立与应用

目的建立小鼠胚胎与配子冷冻库,以安全、有效地保存小鼠资源。方法选择不同遗传背景（近交系、远交群、免疫缺陷、疾病模型和基因改变等）的实验小鼠,系统进行了超数排卵、体外受精（IVF）率、胚胎与精子的冷冻复苏效果、卵巢冷冻与移植、辅助体外受精等比较研究。结果①小鼠年龄和遗传背景的不同,其超数排卵的结果也不同（P〈0．01）。三个日龄段中,28日龄最好,其次为112日龄,56日龄最差;不同遗传背景小鼠的超数排卵结果显示,封闭群和大部分近交系小鼠优于转基因小鼠（P〈0．05）,自发性疾病小鼠和基因剔除小鼠的结果最差;②不同品系小鼠的新鲜精子和冻融精子的体外受精率差异有显著性（P〈0．05）,特别是C57BL／6J小鼠冻融精子的IVF率（10．3±4．2％）与新鲜精子（89．8±4.8％）相比,差异极显著（P〈0．01）;③不同品系小鼠的胚胎复苏率,除MRL／mp小鼠的复苏率略低外,其他小鼠品系均有较高的冷冻胚胎复苏率（58．2％～83．9％）,表明,不同遗传背景小鼠之间差异有显著性（P〈0．05）,但均可以达到有效保存小鼠资源的目的。④小鼠的遗传背景、年龄等对小鼠精子的冷冻效果都有影响,采用改良的FERTIUP冷冻保护剂和细胞质内单精注射（ICSI）技术可有效提高以C57BL／6J为背景的基因改变小鼠的精子冷冻复苏率。⑤卵巢冷冻保存可以改善雌性小鼠的繁殖困难或不孕。结论小鼠资源的安全保存,除了长期连续繁殖保种外,最好的或最保险的方法是低温保存。通过将胚胎、配子、卵巢等长期保存在液氮（-196℃）中避免遗传性状的改变,并在将来复苏后获得正常的小鼠后代,以用于生物学和医学等研究。     

Evaluation of Effects of Laboratory Disinfectants on Mouse Gut Microbiota

Disturbances in the gut microbiota are known to be associated with numerous human diseases. Mice have proven to be an invaluable tool for investigating the role of the gut microbiota in disease processes. Nonexperimental factors related to maintaining mice in the laboratory environment are increasingly being shown to have inadvertent effects on the gut microbiota and may function as confounding variables. Microisolation technique is a term used to describe the common biosecurity practice of spraying gloved hands with disinfectant before handling research mice. This practice prevents contamination with pathogenic microorganisms. To investigate if exposure to disinfectants can affect the mouse gut microbiota, C57BL/6 mice were exposed daily for 27 consecutive days to commonly used laboratory disinfectants through microisolation technique. The effects of 70% ethanol and disinfectant products containing chlorine dioxide, hydrogen peroxide, or potassium peroxymonosulfate were each evaluated. Fecal pellets were collected after 7, 14, 21, and 28 d of disinfectant exposure, and cecal contents were collected at day 28. DNA extractions were performed on all cecal and fecal samples, and microbial community structure was characterized using 16S ribosomal RNA amplicon sequencing. Alpha and β diversity metrics and taxon-level analyses were used to evaluate differences in microbial communities. Disinfectant had a small but significant effect on fecal microbial communities compared with sham-exposed controls, and effects varied by disinfectant type. In general, longer exposure times resulted in greater changes in the fecal microbiota. Effects on the cecal microbiota were less pronounced and only seen with the hydrogen peroxide and potassium peroxymonosulfate disinfectants. These results indicate that laboratory disinfectant use should be considered as a potential factor that can affect the mouse gut microbiota.

The assortment of microorganisms that reside in the gastrointestinal tract of humans and animals are commonly referred to as the gut microbiota. Microbial colonization of the human gastrointestinal tract begins soon after birth.⁵⁰ The microbiota develops through interactions with host and environmental factors, reaching an equilibrium that is relatively stable and unique to each individual person.^20,58 The gut microbiota exists in a complex relationship with the health of the host. Benefits of the gut microbiota include fermentation of nondigestible dietary components into energy and nutrient sources, healthy immune system function, normal gastrointestinal motility, and anticancer effects.^21,38 Conversely, numerous diseases have been associated with variations in gut microbiota composition, which affect physiologic function and organ systems throughout the body. These range from diseases of the gastrointestinal tract itself such as with inflammatory bowel diseases to neurologic disorders such as with Parkinson disease, autism, and mood disorders.^48,56 Other conditions associated with the gut microbiota include obesity, type 2 diabetes, rheumatoid arthritis, liver diseases, lung injury, and cardiovascular diseases.^{25,37,41,44,62,69}Mice are valuable models for investigating the mechanisms involved in the associations seen between disease and gut microbial composition. Advantages of using mice for gut microbiota research include considerable scientific data available in mice, the ability to modify and select for specific genotypes, the establishment of experimental techniques that allow for precise control of the gut microbiota, and the ability to control environment factors.^35,47Nonexperimental differences in the housing environments of research mice have been shown to cause significant dissimilarity in the gut microbiota, and therefore these factors must be a critical consideration when designing experiments.³⁵ Environmental factors that have been shown to contribute to alterations in the gut microbiota include temperature, light cycle, diet, source of drinking water, method of water decontamination, bedding material, and static compared with ventilated microisolation caging.^{6,14,15,18,32,68}Most mice housed in biomedical research facilities are SPF, a term which indicates that the mice have been tested and determined to be free of an extensive list of infectious pathogens.⁵² Maintaining the SPF health status of laboratory mice through rigorous adherence to facility-defined biosecurity practices is vital for animal welfare and ensuring the validity and reproducibility of biomedical research studies.²² A standard biosecurity practice is the housing of SPF mice in sanitized or sterilized microisolation cages. When an experiment requires that mice be handled, such as for injection, gavage, or blood collection, microisolation practices are followed to preserve the aseptic cage environment. These practices include opening of cages inside of a laminar flow station that provides HEPA-filtered air and using disinfectant chemicals to spray the work surface, outer cage, and gloved hands before mice are handled.⁶⁷During microisolation technique handling of mice, some proportion of the disinfectant is inevitably transferred from the gloved hand to the fur of the mice. This disinfectant then becomes a source for oral exposure during normal mouse grooming behavior, which involves repetitive licking of the fur.⁵ Given publications indicating that oral ingestion of other antimicrobials, such as antibiotics and acidified water, result in significant changes to the mouse gut microbiota, we hypothesized that exposure to the disinfectant chemicals used in microisolation technique may affect the gut microbiota as well.^6,63 Oxidizing agents are often the disinfectant category of choice for use in this capacity as they are fast acting and broad spectrum with efficacy against the range of infectious agents of concern to SPF rodent facilities.^1,22 Ethanol, a denaturant disinfectant found ubiquitously in biomedical research laboratories, is not effective against several important nonenveloped viruses and as such is not an ideal choice for use in biosecurity practices.^22,31The primary objective of the current study was to determine if the use of disinfectant during standard microisolation handling of mice can influence the mouse gut microbiota. Differences in the gut microbial composition of mice exposed to 3 commercially available oxidizing agent formulations or a solution of 70% ethanol were evaluated by measuring community-level biodiversity metrics and taxon-level analyses. Effects on ⟨ diversity were assessed by differences in metrics including richness, which quantifies the average number of taxa represented in a microbial community, and Shannon index, which accounts for average taxonomic abundance in addition to richness.^53,55 Effects on β diversity, which describes the differences in total microbial community structure between groups, was assessed using Bray-Curtis dissimilarity.⁵³ In addition, differences in the relative abundance of individual microbial taxa between groups were assessed using the software package edgeR. A secondary objective of this study was to determine whether exposures to these disinfectants resulted in histologic lesions in the skin, gastrointestinal tract, or other tissues. The purpose of this research was to provide insight for institutions and investigators that use these disinfectants for maintaining biosecurity when handling SPF laboratory research mice.     

Neuroethology and life history adaptations of the elasmobranch electric sense.

The electric sense of elasmobranch fishes (sharks and rays) is an important sensory modality known to mediate the detection of bioelectric stimuli. Although the best known function for the use of the elasmobranch electric sense is prey detection, relatively few studies have investigated other possible biological functions. Here, we review recent studies that demonstrate the elasmobranch electrosensory system functions in a wide number of behavioral contexts including social, reproductive and anti-predator behaviors. Recent work on non-electrogenic stingrays demonstrates that the electric sense is used during reproduction and courtship for conspecific detection and localization. Electrogenic skates may use their electrosensory encoding capabilities and electric organ discharges for communication during social and reproductive interactions. The electric sense may also be used to detect and avoid predators during early life history stages in many elasmobranch species. Embryonic clearnose skates demonstrate a ventilatory freeze response when a weak low-frequency electric field is imposed upon the egg capsule. Peak frequency sensitivity of the peripheral electrosensory system in embryonic skates matches the low frequencies of phasic electric stimuli produced by natural fish egg-predators. Neurophysiology experiments reveal that electrosensory tuning changes across the life history of a species and also seasonally due to steroid hormone changes during the reproductive season. We argue that the ontogenetic and seasonal variation in electrosensory tuning represent an adaptive electrosensory plasticity that may be common to many elasmobranchs to enhance an individual's fitness throughout its life history.