There are pros and cons with the traditional model of peer review but authors and researchers benefit from having their paper improved and their knowledge developed. Reviewers also benefit from being able to read cutting edge research prior to publication and before anyone else in the field. They also have the satisfaction of knowing that they are contributing directly to the development of their chosen field. There are numerous different types of peer review, each has its own limitations but SAGE works with our publishing partners to safeguard peer review integrity.
Unfortunately the peer review process is not a perfect one and it is open to manipulation. SAGE takes issues of copyright infringement, plagiarism or other breaches of best practice in publication very seriously. We seek to protect the rights of our authors and we always investigate claims of plagiarism or misuse of published articles. There is a crisis in pre-clinical research. Too many experiments are giving results which turn out to be irreproducible.
This is used in clinical trials where patients are not readily available. But it lacks power and is susceptible to bias, so is unsuitable for pre-clinical experiments where uniform animals are readily available. Each block consists of a set of matched individuals, each receiving a different treatment.
Each block is randomized separately. Blocks will normally be separated in time. This design is powerful, resistant to bias, operationally convenient, and reproducibility can be assessed by comparing the individual blocks.
The RB is the most widely used design in agriculture and industry. The funding organizations have an interest in ensuring that pre-clinical experiments give reproducible results. They should make the RB the default experimental design in pre-clinical research. Use of any other design would need to be specifically justified. Laboratory Animals is the international journal of laboratory animal science, technology, welfare and medicine, LA publishes peer-reviewed original papers and reviews on all aspects of the care and use of animals in research.
Currently, only a third of all submitted manuscripts can be published and we have to be very selective. Therefore, we have to apply high standards for reporting LA research data. The decision to reject manuscripts is not taken lightly, given that for many reports animals were subject to suffering or were sacrificed.
The list is extensive, with flawed experimental design, insufficient animal number, unnecessary suffering or a sex bias. Much of such mistakes could be prevented by a thorough scrutiny of research proposals and licensing review. Methodological flaws, lacking analgesia or wrong anesthesia, or lacking scoresheets and interruption criteria raise ethical concerns and make a publication impossible.
When sever suffering is involved, humane endpoints are mandatory. When only one sex of animals is used, it is difficult to call it an animal model and sex bias may be considered. The review process needs to be fair and objective, and depends on responsible reporting. With increasing pressure to publish, false reporting and suspicion of scientific misconduct cannot be excluded, but such behavior is inacceptable. In conclusion, the number of submissions is increasing every year, while printing space is limited. Therefore, this puts pressure not only authors but also on granting agencies to look at the experimental design and on veterinary authorities to reinforce ethical review of research projects.
Jan-Bas Prins 1 , F. Benavides 2 , T. Ruelicke 3 , J. Bussell 4 , F.
Scavizzi 5 , P. Cinelli 6 , Y. Herault 7 and D. Wedekind 8. Genetic quality assurance QA , including genetic monitoring GeMo of inbred strains and background characterization BC of genetically altered GA animal models, should be an essential component of any QA programme in laboratory animal facilities. Genetic quality control is as important for ensuring the validity of the animal model as health and microbiology monitoring are.
It should be required that studies using laboratory rodents, mainly mice and rats, utilize genetically defined animals. The main goals of any genetic QA programme are: i to verify the authenticity and uniformity of inbred stains and substrains, thus ensuring a genetically reliable colony generation-over-generation; ii to detect possible genetic contamination; and iii to precisely describe the genetic composition of GA lines. There are also efforts ongoing to test and utilize new advancements within the field such as injection method, synthetic gRNAs, … to improve the efficiency of generating these mouse models.
A main part of my work focuses on generating mouse models to study human diseases. Deletions, duplications and inversions of large genomic regions covering several genes are an important class of disease causing variants in humans. Modelling these structural variants in mice required multi-step processes in ES cells, which has limited their availability. We demonstrated before that it is possible to directly generate deletions, duplications and inversions of over one million base pairs by injection of Cas9 into mouse zygotes.
We followed up on this study and are now able to show that thorough analysis of these mice for both small critical exon deletions as well as larger rearrangements is required in order to fully understand the complexity of the alleles present within each F0 founder animal and resulting mouse line. Genetic monitoring is an important aspect of animal quality that is often disregarded and when overlooked, it may negatively impact scientific research. There are many aspects of genetic quality that need to be considered when establishing a genetic monitoring program in a breeding colony, especially when working with genetically modified mice or rats.
ICLAS is aware of this problem and provides training sessions in several scientific venues on this topic. Additionally, it has implemented the genetic monitoring reference program for animal facilities who want to verify the genetic background of the strains they are breeding. We will discuss critical steps to establish a genetic monitoring program on inbred, outbred and genetically modified mice or rats. Exclusion of pathogens has been central in the standardization of laboratory rodents and remains to be important in biomedical research.
However, while a century ago scientists were mainly concerned of spontaneous diseases, we are currently confronted with potential loss of phenotype after rederivation procedures as well as complaints about reproducibility or translational success. Microbiome sequencing shed light into this observation and we know that hygienic standardization came with the risk for limiting the variation of the intestinal microbiome.
While the way back to undefined mice has been of great value for defined studies, large scale application certainly raises profound ethical concerns. This session is intended to open the discussion about how to use current knowledge about the microbiome to constantly enhance the value of biomedical research in the sense of the 3Rs. The creation of well-defined and highly controlled conditions are an essential requirement for ensuring high reproducibility of experimental findings made in laboratory mice.
A key part of this standardization is the control of the hygiene status. Here significant progress had been made over the last decades and the use of tightly controlled barrier facilities, embryo-transfer requirements for importing mice into facilities, have become widely enforced standards. As a consequence, the widely held view among regulatory authorities and those involved in management of animals that increasing the exclusion of microorganisms results in better experimental conditions has been strictly enforced. This greatly affects not only the activity of the immune system, but far beyond.
In fact, a number of significant insights were obtained over the last years showing how pathogen pre-exposed hosts respond compared to our gold-standard laboratory mice. Moreover, we are becoming increasingly aware how microbial and microbiome derived stimuli directly, or in trans through immune cells, impact normal organ physiology. The purpose of the presentation is to briefly summarize some of these findings and to make a strong statement that cleaner is not always better. Instead, it seems more important to improve our ability to describe the particular conditions under which data were obtained, rather than to call for uniform conditions under which experiments can only be performed.
Variability is an important principle of evolutionary biology and we focus our research on wild house mice Mus musculus and their variable genomes. We caught the mice on farms and horse barns and established a wild mice husbandry in an open cage system with ten different populations of wild mice from different origins in the world.
I will describe the needs of wild mice to be considered in the daily husbandry and how to establish a balance between the demands of wild mice to their environment and good laboratory practice. Our mouse house includes a SPF facility, gnotobiotic mice and wild mice under one roof, along with a sophisticated hygiene management. I present our 12 year experience in keeping wild house mice within a laboratory environment with the success and drawbacks we encountered.
This will provide an insight into wild mice husbandry and its challenges which have to be met in respect of animal health and welfare. Between the different populations of wild house mice and especially between wild mice and different laboratory mouse strains, we find considerable differences with respect to their microbiota and behaviour. Especially the differences in behaviour compared to laboratory strains make the husbandry of wild mice a special task.
Therefore, special handling skills of caretakers and enrichment of cages are necessary and mandatory for a good culture of care. Several recent studies have demonstrated that the immune system of traditional laboratory mice is relatively immature and undeveloped, resembling that of human infants that have not yet encountered myriad antigens. In contrast, the immune systems of mice obtained from alternative sources such as pet stores or wild-caught Mus musculus are well-developed and resembles that of a typical human adult, raising the question of whether traditional laboratory mice are appropriate translational models in biomedical research.
While pristine, barrier-raised mice and more antigen-experienced mice both clearly have utility and value, there are biosecurity considerations regarding the use of pet store and feral mice in most vivaria. Certain bacterial taxa colonizing the murine gut, including Helicobacter spp. This presentation will provide information on the experimental generation of breeder mice harboring these provocateurs, in the presence or absence of transient viral pathogens, and in the presence of different gut microbial compositions.
Moreover, the downstream influence of these various microbial factors on susceptibility to two commonly used disease models will be described.
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It is now well-recognized that the microbiota plays an important role in the development, immunity and physiology of its mammalian host. Considerable progress has been made in identifying microbes and microbial metabolites that modulate host functions, maintain health or drive pathology. This knowledge has been derived from the characterization of microbiota during development and adult life, during health and disease, using animal and mechanical models to decipher the complex interactions between microbes and host, and to infer causal relationships.
Facing the tremendous complexity of conventional gut microbiota, gnotobiotic animals are powerful tools to decipher relevant molecular interactions between host, microbial populations and pathogens. Of note, gut microbiota host-specificity has been widely shown to influence both microbial colonization and enteric infection outcome, highlighting its crucial role for inter-species molecular interaction studies. The gnotobiotic Oligo-Mouse Microbiota 12 Oligo-MM 12 model harbors twelve bacterial strains all isolated from conventional mouse microbiota and assigned to five major bacterial phyla: Actinobacteria, Bacteroidetes, Firmicutes, Proteobacteria and Verrucomicrobia.
Interestingly, intestinal colonisation of Oligo-MM 12 consortium was stable over time and mouse generations, which represents an important requirement for the establishment of isobiotic mouse lines.