Antagonistic pleiotropy in mice carrying a CAG repeat expansion in the range causing Huntington's disease.

Antagonist pleiotropy, where a gene exerts a beneficial effect at early stages and a deleterious effect later on in an animal's life, may explain the evolutionary persistence of devastating genetic diseases such as Huntington's disease (HD). To date, however, there is little direct experimental evidence to support this theory. Here, we studied a transgenic mouse carrying the HD mutation with a repeat of 50 CAGs (R6/2_50) that is within the pathological range of repeats causing adult-onset disease in humans. R6/2_50 mice develop characteristic HD brain aggregate pathology, with aggregates appearing predominantly in the striatum and cortex. However, they show few signs of disease in their lifetime. On the contrary, R6/2_50 mice appear to benefit from carrying the mutation. They have extended lifespans compared to wildtype (WT) mice, and male mice show enhanced fecundity. Furthermore, R6/2_50 mice outperform WT mice on the rotarod and show equal or better performance in the two choice discrimination task than WT mice. This novel mouse line provides direct experimental evidence that, although the HD mutation causes a fatal neurodegenerative disorder, there may be premorbid benefits of carrying the mutation

Technical note: Validation of an automatic recording system to assess behavioural activity level in sheep (Ovis aries)

The welfare of an individual can be assessed by monitoring behavioural changes, such as inactivity, that may indicate injury or disease. In this study we validated the Actiwatch Mini® activity monitor (AM) for automatic recording of behavioural activity levels of nine Texel ewes. The AM devices were attached to collars placed around the necks of the ewes. AM recordings were taken at 25 second intervals for 21 consecutive days and in addition, direct behavioural observations made on days 9–13. AM recordings were compared with direct behavioural observations to investigate whether different levels of behaviour activity could be distinguished by the AM. Six different behaviours were matched to the activity scores recorded by the AM which were low activity (lying ruminating, lying), medium activity (standing, standing ruminating, and grazing) and high activity behaviours (walking). There were differences in the activity scores for all three scores. However, higher levels of accuracy in distinguishing between activity levels were achieved when combining high and medium activity level behaviours. This method of capturing data provides a practical tool in studies assessing the impact of disease or injury. For example, assessing the effects of lameness on the activity level of sheep at pasture, without the presence of an observer influencing behaviour.The authors thank the staff at the farm, at which data were collected, for supporting the study and for taking good care of the animals. This study was part of a project funded by the EU VII Framework programme Animal Welfare Indicators (Grant no. FP7-KBBE-2010-4) who had no involvement in the study design, data collection, data analysis or writing of the report. The Actiwatches’ were provided to AJM through funding from CHDI Foundation, Inc.This is the author accepted manuscript. The final version is available from Elsevier at http://www.sciencedirect.com/science/article/pii/S0921448815001455

Characterisation of progressive motor deficits in whisker movements in R6/2, Q175 and Hdh knock-in mouse models of Huntington's disease

BACKGROUND: Motor dysfunction is a major component of the Huntington's disease (HD) phenotype, both in patients and animal models. Motor function in mice is usually measured using tests that involve a novel environment, or require a degree of learning, which creates potential confounds in animals, such as anxiety and/or learning. NEW METHOD: We propose that studying whisker control provides a more naturalistic way to measure motor function in HD mice. To this end we tested three strains of HD mice; R6/2 (CAG250), zQ175 and Hdh (CAG50, 150 and 250) mice. RESULTS: We discovered a clear and progressive whisking deficit in the most severe model, the R6/2 CAG250 mouse. At 10 weeks, R6/2 mice showed an increase in whisking movements, which may be a correlate of the hyperkinesia seen in HD patients. By 18 weeks the R6/2 mice showed a reduction in whisking movements. Hdh Q250 mice showed a hyperkinetic profile at 10 weeks, approximately 4 months before other motor deficits have previously been reported in these mice. Q175 mice showed very little change in whisking behaviour, apart from a transient increase in retraction velocity at 10 weeks. COMPARISONS WITH EXISTING METHODS: Our findings suggest that whisking may be a more sensitive test of motor function in HD mice than more commonly used methods, such as the rotarod. CONCLUSIONS: Our data suggest that whisking deficits represent a novel way of assessing the progression of the motor phenotype, and are early indicators for reversal of phenotype studies, such as drug trials.All work was funded via internal grants from the University of Cambridge and Manchester Metropolitan University

“Microbiota, symbiosis and individuality summer school” meeting report

How does microbiota research impact our understanding of biological individuality? We summarize the interdisciplinary summer school on “Microbiota, symbiosis and individuality: conceptual and philosophical issues” (July 2019), which was supported by a European Research Council starting grant project “Immunity, DEvelopment, and the Microbiota” (IDEM). The summer school centered around interdisciplinary group work on four facets of microbiota research: holobionts, individuality, causation, and human health. The conceptual discussion of cutting-edge empirical research provided new insights into microbiota and highlights the value of incorporating into meetings experts from other disciplines, such as philosophy and history of science

Holobionts and the ecology of organisms - Multi-species communities or integrated individuals?

It is now widely accepted that microorganisms play many important roles in the lives of plants and animals. Every macroorganism has been shaped in some way by microorganisms. The recognition of the ubiquity and importance of microorganisms has led some to argue for a revolution in how we understand biological individuality and the primary units of natural selection. The term “holobiont” was introduced as a name for the biological unit made up by a host and all of its associated microorganisms, and much of this new debate about biological individuality has focused on whether holobionts are integrated individuals or communities. In this paper, I show how parts of the holobiont can span both characterizations. I argue that most holobionts share more affinities with communities than they do with organisms, and that, except for maybe in rare cases, holobionts do not meet the criteria for being organisms, evolutionary individuals, or units of selection

Characterisation of progressive motor deficits in whisker movements in R6/2, Q175 and Hdh knock-in mouse models of Huntington's disease

BACKGROUND: Motor dysfunction is a major component of the Huntington's disease (HD) phenotype, both in patients and animal models. Motor function in mice is usually measured using tests that involve a novel environment, or require a degree of learning, which creates potential confounds in animals, such as anxiety and/or learning. NEW METHOD: We propose that studying whisker control provides a more naturalistic way to measure motor function in HD mice. To this end we tested three strains of HD mice; R6/2 (CAG250), zQ175 and Hdh (CAG50, 150 and 250) mice. RESULTS: We discovered a clear and progressive whisking deficit in the most severe model, the R6/2 CAG250 mouse. At 10 weeks, R6/2 mice showed an increase in whisking movements, which may be a correlate of the hyperkinesia seen in HD patients. By 18 weeks the R6/2 mice showed a reduction in whisking movements. Hdh Q250 mice showed a hyperkinetic profile at 10 weeks, approximately 4 months before other motor deficits have previously been reported in these mice. Q175 mice showed very little change in whisking behaviour, apart from a transient increase in retraction velocity at 10 weeks. COMPARISONS WITH EXISTING METHODS: Our findings suggest that whisking may be a more sensitive test of motor function in HD mice than more commonly used methods, such as the rotarod. CONCLUSIONS: Our data suggest that whisking deficits represent a novel way of assessing the progression of the motor phenotype, and are early indicators for reversal of phenotype studies, such as drug trials.All work was funded via internal grants from the University of Cambridge and Manchester Metropolitan University