Nous voulions déterminer les facteurs de l'anthropisation impliqués dans le commensalisme de la souris, selon une approche phylogéographique et historique.<br />La quantification de la variabilité actuelle des morphologies dentaires (analyses de Fourier) du genre Mus en Méditerranée a montré qu'il est possible de discriminer les espèces et sous-espèces du genre à partir du matériel fossile et qu'elle pouvait être un marqueur des flux géniques. <br />L'application archéozoologique nous a permis d'identifier l'émergence des pratiques de l'économie agricole néolithique (stockage des grains, champs cultivés...) au Proche-Orient comme le facteur déterminant dans l'adaptation de la souris à la niche commensale.<br />Enfin, nous avons montré que la souris domestique colonisa la Méditerranée occidentale lors de l'intensification conjointe des échanges et de l'urbanisation du premier millénaire av. J.-C., lui permettant de surmonter les barrières écologiques et génétiques qui, auparavant, empêchaient son invasion.

<p>The genetic basis for behavioural traits is largely unknown. The overall aim of this thesis was to find genes with importance for behavioural traits related to fear and anxiety. Microarray analysis was used to screen expression profiles of brain regions important for emotional behaviour in dogs, wolves, foxes and mice. In a first experiment, dogs and their wild ancestors the wolves were compared. Our results suggested that directed selection for behaviour might have resulted in expression changes in few genes acting on several brain functions, possibly affecting behaviour. However, the observed expressional differences were confounded with environmental effects. This was addressed in a second study on domesticated silver foxes. By correlating behaviour and brain gene expression in foxes selected for tameness to non-selected foxes raised in the same environment, we found large behavioural differences but only few genes with differential expression in the brain. Fifteen of the 40 genes showing evidence of expression difference were related to haem or haemoglobins. Further studies showed an additive genetic effect on brain gene expression, similar to the additive genetic inheritance of behaviour, indicating an involvement in domestication. Transcriptional profiling was also used for finding genes involved with the sleep disorder narcolepsy. Narcoleptic Doberman pinschers homozygous for the canarc-1 mutation were compared to their unaffected heterozygots revealing reduced expression of three genes, TAC1, PENK and SOCS2, with relevance to the narcoleptic phenotype. Finally gene expression was investigated in relation to anxiety-related traits in a mouse model. Surprisingly, as in the fox study, genes coding for haemoglobins indicated differential expression in the brain between animals with different anxiety levels. Our combined results suggest that genes like haemoglobins, best known for their function in oxygen transport in blood, may also participate in brain functions related to decreased anxiety in domestic animals. </p>

The genetic basis for behavioural traits is largely unknown. The overall aim of this thesis was to find genes with importance for behavioural traits related to fear and anxiety. Microarray analysis was used to screen expression profiles of brain regions important for emotional behaviour in dogs, wolves, foxes and mice. In a first experiment, dogs and their wild ancestors the wolves were compared. Our results suggested that directed selection for behaviour might have resulted in expression changes in few genes acting on several brain functions, possibly affecting behaviour. However, the observed expressional differences were confounded with environmental effects. This was addressed in a second study on domesticated silver foxes. By correlating behaviour and brain gene expression in foxes selected for tameness to non-selected foxes raised in the same environment, we found large behavioural differences but only few genes with differential expression in the brain. Fifteen of the 40 genes showing evidence of expression difference were related to haem or haemoglobins. Further studies showed an additive genetic effect on brain gene expression, similar to the additive genetic inheritance of behaviour, indicating an involvement in domestication. Transcriptional profiling was also used for finding genes involved with the sleep disorder narcolepsy. Narcoleptic Doberman pinschers homozygous for the canarc-1 mutation were compared to their unaffected heterozygots revealing reduced expression of three genes, TAC1, PENK and SOCS2, with relevance to the narcoleptic phenotype. Finally gene expression was investigated in relation to anxiety-related traits in a mouse model. Surprisingly, as in the fox study, genes coding for haemoglobins indicated differential expression in the brain between animals with different anxiety levels. Our combined results suggest that genes like haemoglobins, best known for their function in oxygen transport in blood, may also participate in brain functions related to decreased anxiety in domestic animals.

Retrogenes are functional genes that are created through retroposition, whereby mature mRNA is reverse-transcribed and re-integrated into the genome. In this study, the following objectives were accomplished: (i) intrachromosomal- and interchromosomal-retroposed genes were located in H. sapiens, (ii) interchromosomal-retroposed genes were located in M. musculus, D. melanogaster, and C. elegans. To date, this is the first assay for intrachromosomal-retroposed genes in H. sapiens and interchromosomal-retroposed genes in C. elegans. Biases discovered include excess interchromosomal generation of retrogenes by chromosome X in H. sapiens, M. musculus, and D. melanogaster. Selection pressure created by the inactivation of the X chromosome during male meiosis appears to be at least partially responsible for this phenomenon. In addition, excess interchromosomal recruitment of retrogenes by chromosome X was observed in H. sapiens. The driving force appears to be an interplay between selection for female-beneficial genes and selection for male-beneficial genes. No other chromosome biases were discovered.

Retrogenes are functional genes that are created through retroposition, whereby mature mRNA is reverse-transcribed and re-integrated into the genome. In this study, the following objectives were accomplished: (i) intrachromosomal- and interchromosomal-retroposed genes were located in H. sapiens, (ii) interchromosomal-retroposed genes were located in M. musculus, D. melanogaster, and C. elegans. To date, this is the first assay for intrachromosomal-retroposed genes in H. sapiens and interchromosomal-retroposed genes in C. elegans. Biases discovered include excess interchromosomal generation of retrogenes by chromosome X in H. sapiens, M. musculus, and D. melanogaster. Selection pressure created by the inactivation of the X chromosome during male meiosis appears to be at least partially responsible for this phenomenon. In addition, excess interchromosomal recruitment of retrogenes by chromosome X was observed in H. sapiens. The driving force appears to be an interplay between selection for female-beneficial genes and selection for male-beneficial genes. No other chromosome biases were discovered.

A variety of prey species are able to detect predators by odours emanating from their urine, feces, fur and anal glands. However, it is unknown whether the odour of a predator’s blood also contains information signalling “predator” to a prey. The aim of the present study was therefore to assess if blood odour from a cat elicits avoidance or anxiety responses in CD-1 mice (Mus musculus). A two-compartment test arena was used to assess place preference, motor activity and fecal excretions when the mice were simultaneously presented with cat blood and a blank control. Additionally, the mice were tested with horse blood and N-pentyl acetate, a fruity odour. The mice did not show avoidance of any of the three odours. Nevertheless, the mice were significantly less active when exposed to cat blood in comparison to horse blood, but did not increase defecation when exposed to cat blood. This suggests that the information mice get by the odour of cat blood did not contain the signal “predator”.

It is essential for prey species to be able to detect predators to avoid them. The sense of smell is used by a number of prey species for this purpose. The aim of the present study was to assess if one of the odourants that make up a predator odour is sufficient to induce a behavioural response in mice (Mus musculus). Two predator odourants were used, 2,2-dimethylthietane and methyl-2-phenylethyl sulfide, which are both found in the secretions of natural predators of mice. An odourant found in fruits, n-pentyl acetate, was also used. All three odourants were presented at a concentration that was a factor of 100 above the olfactory detection threshold of mice. Ten adult predator-naïve CD-1 mice were individually put in a two-compartment chamber one of which contained an odourant while the other contained a near-odourless solvent (diethyl phthalate). The results indicated that methyl-2-phenylethyl sulfide was actively avoided by the mice. Towards 2,2-dimethylthietane and n-pentyl acetate, in contrast, the mice behaved indifferent. Further, the results suggest a significant correlation between the number of switches between the two compartments of the test chamber and the test sessions when the animals were presented with n-pentyl acetate, but not when they were presented with the predator odourants. The results support the notion of an innate fear response towards the predator odourant methyl-2-phenylethyl sulfide in mice, but further studies with more animals and different concentrations of the odourants are necessary.

Speciation, the formation of new species, is an essential evolutionary process that causes species diversity on the Earth. At the beginning of this process is the separation of two populations by a reproductive barrier that prevents gene flow between these populations. One of the mechanisms, which enable reproductive isolation, is hybrid sterility (HS). It is a mechanism of postzygotic isolation that is described in a number of eukaryotes. The first discovered gene of hybrid sterility in vertebrates is the mice gene Hst1, later identified as gene Prdm9. By genetic and molecular analysis the locus on the X chromosome was determined, whose interaction with Prdm9 causes sterility or reduced fitness in male hybrids. This locus contains two genetic factors: Hstx1, causing an abnormal morphology of spermatozoa, and Hstx2, causing an arrest in spermatogenesis in pachytene spermatocytes and sterility. In my thesis I focus on the effect of deletion of a candidate hybrid sterility gene Fmr1nb on the X chromosome. The analysis of males B6N.Fmr1nbmut with deletion variants of the Fmr1nb gene showed that Fmr1nb is one of the factors influencing spermatogenesis. An increase in morphologic abnormalities in spermatozoa occurred in males with Fmr1nb gene deletion. This phenotype is identical with Hstx1. The effect...

Sertoli cells (SCs) are somatic cells of testicular tissue that are involved in spermatogenesis and maturation of germ cells. They are currently being extensively studied for their immunomodulatory abilities, and recent studies have shown that they share some properties with mesenchymal stromal cells (MSCs). Detailed characterization of SCs and clarification of their role in testicular tissue is crucial for potential use of SCs as a therapeutic tool in regenerative medicine. Cell culture of Xenopus tropicalis immature Sertoli cells (XtiSCs) and Mus musculus (mSCs) Sertoli cells were established in the Laboratories of Developmental Biology and Immunoregulations, Faculty of Science, Charles University. Previous research has characterized XtiSCs and demonstrated their multipotent potential by in vitro differentiation into a mesodermal line. Following this research, one of the goals of the diploma project was the induction of in vitro differentiation of XtiSC into other cell types, which would verify the differentiation potential of XtiSCs. The mSC expression profile confirmed the somatic origin of this culture as well as the transcription of Sertoli cell gene markers. Differentiation of mSCs along the mesodermal line into osteoblasts, chondrocytes and adipocytes has been successfully induced in vitro....

<p> The age at which a juvenile female reaches sexual maturity can be modulated by a variety of environmental and social factors. Experiments described in this thesis were designed to enhance the current understanding of the relationships among three variables that influence the onset of sexual maturation in female mice (Mus musculus), including: [1] exposure to dietary phytoestrogens during development, [2] variations in prenatal androgens, and [3] the presence or absence of genetically-unrelated males after weaning. For the first time, age at onset of male-induced female puberty was investigated using non-invasive behavioural and fertility measures. Through enzyme immunoassay procedures, daily output of urinary creatinine, 17P-estradiol, and progesterone was profiled in developing females that were either isolated or exposed to adult males. Uterine and ovarian tissue was also measured in such females, and male exposure was observed to increase reproductive tissue mass and was influenced by prior androgen exposure in interaction with diet and male presence. Male-exposed females fed a diet containing phytoestrogens immediately became sexually receptive when housed directly with males, and they conceived earlier than females in other conditions. Females with longer anogenital distance, which reflects higher in utero androgen exposure, displayed more escape attempts and aggressive posturing in the direct presence of males, especially when they had been housed near males and fed the phytoestrogen-containing diet. Urinary 17P-estradiol was substantially reduced in females raised on the phytoestrogenfree diet. Urinary output of progesterone was not strongly influenced by diet. Maleexposed females ' output of progesterone and 17P-estradiol was more dynamic in comparison to that of isolated females. The size of this effect depended on diet, prior androgen exposure, and whether urinary steroid measures were adjusted by urinary creatinine. Urinary creatinine was elevated by the low phytoestrogen diet and reduced by male exposure. These data suggest that dietary phytoestrogens and in utero androgen exposure interact with presence or absence of males in determining the age at onset of sexual maturity in developing females. </p> <p> A final experiment was designed to examine two components of adult male urine, preputial gland emissions and unconjugated estrogens, that have been posited to act on females to advance reproductive maturation. Intact and preputialectomized males were compared in their output of urinary creatinine, 17~-estradiol, and testosterone, and in their influence on reproductive tissue in juvenile females. Lack of preputial glands did not hinder the capacity of males to induce uterine and ovarian growth in females. Male urinary creatinine was reduced by exposure to juvenile females. Creatinine-adjusted 17~estradiol and testosterone were greater in female-exposed males, regardless of whether the preputial glands were present. Based on these findings and those reported elsewhere, it is probable that male excreted urinary steroids are important in regulating reproductive changes in developing females exposed to males. </p> / Thesis / Doctor of Philosophy (PhD)