Heterogeneity of the coumarin anticoagulant targeted vitamin K epoxide reduction system. Study of kinetic parameters in susceptible and resistant mice (Mus musculus domesticus)

Vitamin K epoxide reductase (VKOR) activity in liver microsomes from a susceptible and a genetically warfarin-resistant strain of mice (Mus Musculus domesticus) was analyzed to determine the mechanism of resistance to this 4-hydroxycoumarin derivative. Kinetic parameters for VKOR were calculated for each strain by incubating liver microsomes with vitamin K epoxide +/- warfarin. In susceptible mice, an Eadie-Hofstee plot of the data was not linear and suggested the involvement of at least two different components. Apparent kinetic parameters were obtained by nonlinear regression using a Michaelis--Menten model, which takes into account two enzymatic components. Component A presents a high Km and a high Vm, and as a consequence only an enzymatic efficiency Vm/Km was obtained (0.0024 mL/min/mg). Estimated warfarin Ki was 0.17 microM. Component B presented an apparent Km of 12.73 microM, an apparent Vm of 0.32 nmol/min/mg, and an apparent Ki for warfarin of 6.0 microM. In resistant mice, the enzymatic efficiency corresponding to component A was highly decreased (0.0003-0.00066 mL/min/mg) while the Ki for warfarin was not modified. The apparent Vm of component B was poorly modified between susceptible and resistant mice. The apparent Km of component B observed in resistant mice was similar to the Km observed in susceptible mice. These modifications of the catalytic properties are associated with a single nucleotide polymorphism (T175G) in the VKOR-C1 gene, which corresponds to a Trp59Gly mutation in the protein.     

An analysis of signatures of selective sweeps in natural populations of the house mouse

Population and locus-specific reduction of variability of polymorphic loci could be an indication of positive selection at a linked site (selective sweep) and therefore point toward genes that have been involved in recent adaptations. Analysis of microsatellite variability offers a way to identify such regions and to ask whether they occur more often than expected by chance. We studied four populations of the house mouse (Mus musculus) to assess the frequency of such signatures of selective sweeps under natural conditions. Three samples represent the subspecies Mus m. dometicus [corrected] and came from Germany, France, and Cameroon. One sample came from Kazakhstan and constitutes a population of the subspecies Mus m. [corrected] musculus. Mitochondrial D-loop sequences from all animals confirm their respective assignments. Approximately 200 microsatellite loci were typed for up to 60 unrelated individuals from each population and evaluated for signs of selective sweeps on the basis of Schl?tterer's ln RV and ln RH statistics. Our data suggest that there are slightly more signs of selective sweeps than would have been expected by chance alone in each of the populations and also highlights some of the statistical challenges faced in genome scans for detecting selection. Single-nucleotide polymorphism typing of one sweep signature in the M. m. domesticus populations around the beta-defensin 6 locus confirms a lowered nucleotide diversity in this region and limits the potential sweep region to about 20 kb. However, no amino acid exchange has occurred in the coding region when compared to M. m. musculus. If this sweep signature is due to a recent adaptation, it is expected that a regulatory change would have caused it. Our data provide a framework for conducting a systematic whole genome scan for signatures of selective sweeps in the mouse genome.     

Does the house mouse self-regulate its density in maturing sorghum and wheat crops?

1. One of the central questions in population ecology and management is: what regulates population growth? House mouse Mus domesticus L. populations erupt occasionally in grain-growing regions in Australia. This study aimed to determine whether mouse populations are self-regulated in maturing sorghum and wheat crops. This was assessed by examining food supply to mice (i.e. yield) and the relationship between initial mouse density (D(I)) and density at harvest (D(H)). Eight levels of D(I) ranging from 89 to 5555 mice ha(-1) were introduced to sorghum at the hard dough stage and to wheat crops at the milky stage in mouse-proofed pens. D(H) was measured by trapping out mice 49 days after the introduction. 2. There were at least 3.11 tonnes ha(-1) of wheat and 1.85 tonnes ha(-1) of sorghum grain available for mice at harvest. The estimated relationship between D(I) and D(H) was asymptotic exponential, with D(H) initially increasing almost linearly with D(I). When D(I) was above c. 500 mice ha(-1), D(H) increased asymptotically with D(I) and then saturated at c. 3100 mice ha(-1). The asymptotic increases in and saturation of D(H) was due partly to more young mice being born and recruited in pens treated with lower levels of D(I). 3. Our findings indicated that mouse densities in maturing cereal crops were driven by a numerical response of mice to the abundant supply of grain, modified by some unknown self-regulation mechanism that reduced this numerical response of mice at higher mouse densities. The mechanism was possibly spacing behaviours. Although the nature of this self-regulation mechanism is not known our model is, nevertheless, useful for predicting increases and eruptions in mouse population density in sorghum and wheat crops. Understanding the nature of this mechanism may provide insights into population processes that can be exploited in controlling mice in cereal crops.     

A potential multivariate index of condition for small mammals

Abstract

Post‐weaning growth rates were measured for juvenile house mice (Mus domesticus) reared under four experimental treatments representing dietary conditions in cereal‐growing areas of southeastern Australia. The mice were bred in captivity from adult wild mice captured in mature dry cereal crops during summer. Juvenile mice were caged in pairs at 23°C and offered a diet of either ripening wheat heads or mature dry wheat heads, with or without access to free water. All diets were adequate for survival, but juvenile mice on a diet of ripening wheat with water available grew at 0.25 g day–1, 260% faster than those on a diet of mature wheat and deprived access to free water. Mice on a diet of ripening wheat but deprived of free water and those on a diet of mature wheat with water available grew at intermediate rates. Post‐weaning growth rates of mice in all treatment groups were higher when the young were weaned at higher body mass. The results have implications for estimates of growth, timing of sexual maturity and reproduction of mice in field populations, and indicate that prolonged access to ripening grain and/or relief from moisture stress are likely to be critical to rapid population increase during population outbreaks.     

Assessing multilocus introgression patterns: a case study on the mouse X chromosome in central Europe

Multilocus hybrid zone (HZ) studies predate genomics by decades. The power of early methods is becoming apparent and now large datasets are commonplace. Relating introgression along a chromosome to evolutionary process is challenging: although reduced introgression regions may indicate speciation genes, this pattern may be obscured by asymmetric introgression of linked invasive genes. Further, HZ movement may form salients and leave islands in its wake. Barton's concordance was proposed 24 years ago for assessing introgression where geographic patterns are complex. The geographic axis of introgression is replaced with the hybrid index. We compare this, a recently proposed genomic clines approach, and two-dimensional (2D) geographic analyses, for 24 X chromosome loci of 2873 mice from the central-European house mouse HZ. In 2D, 14 loci show linear contact, seven precisely matching previous studies. Four show introgression islands to the east of the zone, suggesting past westward zone movement, two show westward salients. Barton's concordance both recovers and refines this information. A region of reduced introgression on the central X is supported, despite X centromere-proximal male-biased westward introgression matching a westward 2D geographic salient. Genomic clines results are consistent regarding introgression asymmetries, but otherwise more difficult to interpret. Evidence for genetic conflict is discussed.     

House mouse dispersal in Iron Age Spain: a geometric morphometrics appraisal

During the Iron Age, sea trade in the Mediterranean increased, particularly with the expansion of Phoenician and Greek colonies in the Western Mediterranean. A side effect of these human movements was the involuntary dispersion of commensal species, such as the house mouse (Mus musculus domesticus). One archaeological layer dated from the 4th Century BC, coming from an Iberian village located in the Mediterranean coast of Spain, contained a large and reliable accumulation of small mammals. The presence of the house mouse was highly suspected within this layer. To assess its abundance quantitatively, we used a geometric morphometrics approach of the first lower molar contour using elliptical Fourier analysis. We also increased the power of the discrimination between the Algerian mouse (Mus spretus) and the house mouse by combining a dimension reduction approach together with different validation procedures. The relative importance of age, sex, and geographical origin onto the shape and form of the lower molar contour was also investigated. The results obtained demonstrate the presence and the dominance of the house mouse in the landscape surrounding the Iberian village in the 1st Millennium BC, only a few centuries after its arrival in the Western Mediterranean Basin. A cross‐validated linear discriminant function considering different Mediterranean populations suggest Morocco and France as the most probable geographical origins for the Algerian mouse, and Tunisia for the origin of house mice in North‐Eastern Spain. © 2011 The Linnean Society of London, Biological Journal of the Linnean Society, 2011, 102 , 483–497.     

Hard to fly the nest： A study of body condition and plumage quality in house sparrow fledglings

Contrary to the nestling phase, the post-fledging phase has been less studied probably because it is challenging to follow the chicks after they fledge. However, this phase is crucial to consider when focusing on the life cycle of individuals because it is associated with new demands： After leaving the nest, individuals have to find their own food and cope with a new set of previously unknown stressors. In this study, we aimed at better understanding how energetically demanding the post-ftedging period is in house sparrows Passer domesticus by measuring several indices of a fledgling＇s state （body condition, fat and muscle scores and plumage quality）. If the energetic demands of the post-fledging period are greater than those of the adult life, we predicted that fledglings should be in lower condition and should have a plumage of lower quality relative to adults. Supporting this prediction, the condition and the plumage of fledglings differed dramatically from those of adults. Interestingly, this difference disappeared in autumn. Overall, our results suggest that the post-fledging period is probably one of the most energetically demanding of the life cycle in this species. Supporting this idea, the resighting probability of fledglings was lower relative to adults. However, resighting probability depends on many factors （mortality, dispersal, habitat use and behaviours） and future studies are necessary to tease apart their relative importance in determining resighting probability [Current Zoology 60 （4）： 449-459, 2014].     

Balbiani bodies in cricket oocytes: Development, ultrastructure, and presence of localized RNAs

Formation of two spherical Balbiani bodies along the long axis of previtellogenic oocytes in Acheta domesticus was demonstrated by differential interference microscopy. The structures form adjacent to and on opposite sides of the germinal vesicle, the anterior body first. Each migrates to the nearest pole of the elongating oocyte and retains its spherical structure until occluded from view by accumulating yolk. In situ hybridization, immunocytochemistry, and confocal immunofluorescent microscopy showed Balbiani body components to include y-tubulin, alpha-tubulin, EF1alpha, and several RNAs homologous to localized Xenopus RNAs implicated in embryonic axis formation or germ cell determination. The latter include Xcat2, Xwnt11, Xlsirt, and Xpat. Balbiani body ultrastructure includes a dense cloud of tubular mitochondria, rough ER, Golgi-like membrane aggregates, and microtubules. The results suggest that molecules and mechanisms specifying early determinative events for embryogenesis in vertebrates and insects are highly conserved and that Balbiani bodies may have a role in establishing developmental asymmetry in the cricket.     

Fast evolutionary response of house mice to anthropogenic disturbance on a Sub‐Antarctic island

Invasions and anthropogenic disturbances challenge species with rapid environmental changes. Understanding how organisms respond to these changes is of major concern for the future of biodiversity. The house mouse on a Sub‐Antarctic island (Guillou Island, Kerguelen Archipelago) had to face such challenges twice: first when invading the island two centuries ago; and nowadays when coping with an in‐depth remodeling of its habitat due to a cohort of anthropogenic changes. Morphometric and biomechanical results show that the initial invasion triggered the evolution of a jaw shape adapted to the local food resources. Contemporary changes are also associated to changes in jaw morphology, but are not directly functionally relevant. Here, a complex response integrating feeding behaviour, investment in feeding structure, and degree of mineralization, may provide the mice with a better tool to benefit of wider resources utilization and/or better cope with intra‐specific competition in a changing habitat. These Sub‐Antarctic mice exemplify that success of invasive species rely on the capacity of facing rapidly varying environments through integrated, multi‐faceted responses involving behaviour to morphology through life‐history traits. © 2015 The Linnean Society of London, Biological Journal of the Linnean Society, 2015, 114 , 513–526.