- MeSH
- genetické inženýrství metody MeSH
- geneticky modifikované organismy * genetika MeSH
- genová knihovna MeSH
- geny genetika MeSH
- interdisciplinární výzkum metody MeSH
- myši genetika MeSH
- výzkum MeSH
- Check Tag
- myši genetika MeSH
- Publikační typ
- novinové články MeSH
- Geografické názvy
- Česká republika MeSH
The classical definition posits hybrid sterility as a phenomenon when two parental taxa each of which is fertile produce a hybrid that is sterile. The first hybrid sterility gene in vertebrates, Prdm9, coding for a histone methyltransferase, was identified in crosses between two laboratory mouse strains derived from Mus mus musculus and M. m. domesticus subspecies. The unique function of PRDM9 protein in the initiation of meiotic recombination led to the discovery of the basic molecular mechanism of hybrid sterility in laboratory crosses. However, the role of this protein as a component of reproductive barrier outside the laboratory model remained unclear. Here, we show that the Prdm9 allelic incompatibilities represent the primary cause of reduced fertility in intersubspecific hybrids between M. m. musculus and M. m. domesticus including 16 musculus and domesticus wild-derived strains. Disruption of fertility phenotypes correlated with the rate of failure of synapsis between homologous chromosomes in meiosis I and with early meiotic arrest. All phenotypes were restored to normal when the domesticus Prdm9dom2 allele was substituted with the Prdm9dom2H humanized variant. To conclude, our data show for the first time the male infertility of wild-derived musculus and domesticus subspecies F1 hybrids controlled by Prdm9 as the major hybrid sterility gene. The impairment of fertility surrogates, testes weight and sperm count, correlated with increasing difficulties of meiotic synapsis of homologous chromosomes and with meiotic arrest, which we suppose reflect the increasing asymmetry of PRDM9-dependent DNA double-strand breaks.
- MeSH
- fylogeografie MeSH
- genová introgrese * MeSH
- histonlysin-N-methyltransferasa genetika MeSH
- infertilita genetika MeSH
- meióza MeSH
- myši genetika MeSH
- reprodukční izolace * MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši genetika MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Zebrafish (Danio rerio) is a valuable non-mammalian vertebrate model widely used to study development and disease, including more recently cancer. The evolutionary conservation of cancer-related programs between human and zebrafish is striking and allows extrapolation of research outcomes obtained in fish back to humans. Zebrafish has gained attention as a robust model for cancer research mainly because of its high fecundity, cost-effective maintenance, dynamic visualization of tumor growth in vivo, and the possibility of chemical screening in large numbers of animals at reasonable costs. Novel approaches in modeling tumor growth, such as using transgene electroporation in adult zebrafish, could improve our knowledge about the spatial and temporal control of cancer formation and progression in vivo. Looking at genetic as well as epigenetic alterations could be important to explain the pathogenesis of a disease as complex as cancer. In this review, we highlight classic genetic and transplantation models of cancer in zebrafish as well as provide new insights on advances in cancer modeling. Recent progress in zebrafish xenotransplantation studies and drug screening has shown that zebrafish is a reliable model to study human cancer and could be suitable for evaluating patient-derived xenograft cell invasiveness. Rapid, large-scale evaluation of in vivo drug responses and kinetics in zebrafish could undoubtedly lead to new applications in personalized medicine and combination therapy. For all of the above-mentioned reasons, zebrafish is approaching a future of being a pre-clinical cancer model, alongside the mouse. However, the mouse will continue to be valuable in the last steps of pre-clinical drug screening, mostly because of the highly conserved mammalian genome and biological processes.
- MeSH
- dánio pruhované genetika MeSH
- druhová specificita MeSH
- epigeneze genetická MeSH
- geneticky modifikovaná zvířata genetika MeSH
- lidé MeSH
- modely nemocí na zvířatech MeSH
- mutace MeSH
- myši genetika MeSH
- nádorové biomarkery genetika MeSH
- nádorové buněčné linie MeSH
- nádory genetika MeSH
- regulace genové exprese u nádorů * MeSH
- sekvenování celého genomu MeSH
- technika přenosu genů MeSH
- xenogenní modely - testy antitumorózní aktivity MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši genetika MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
Hematopoiesis in mammalian embryos proceeds through three successive waves of hematopoietic progenitors. Since their emergence spatially and temporally overlap and phenotypic markers are often shared, the specifics regarding their origin, development, lineage restriction and mutual relationships have not been fully determined. The identification of wave-specific markers would aid to resolve these uncertainties. Here, we show that toll-like receptors (TLRs) are expressed during early mouse embryogenesis. We provide phenotypic and functional evidence that the expression of TLR2 on E7.5 c-kit+ cells marks the emergence of precursors of erythro-myeloid progenitors (EMPs) and provides resolution for separate tracking of EMPs from primitive progenitors. Using in vivo fate mapping, we show that at E8.5 the Tlr2 locus is already active in emerging EMPs and in progenitors of adult hematopoietic stem cells (HSC). Together, this data demonstrates that the activation of the Tlr2 locus tracks the earliest events in the process of EMP and HSC specification.
- MeSH
- dospělé kmenové buňky metabolismus MeSH
- hematopoetické kmenové buňky metabolismus MeSH
- hematopoéza MeSH
- myši inbrední C57BL MeSH
- myši embryologie genetika metabolismus MeSH
- protoonkogenní proteiny c-kit genetika metabolismus MeSH
- toll-like receptor 2 genetika metabolismus MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši embryologie genetika metabolismus MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The Wnt, TGF-β, and Notch signaling pathways are essential for the regulation of cellular polarity, differentiation, proliferation, and migration. Differential activation and mutual crosstalk of these pathways during animal development are crucial instructive forces in the initiation of the body axis and the development of organs and tissues. Due to the ability to initiate cell proliferation, these pathways are vulnerable to somatic mutations selectively producing cells, which ultimately slip through cellular and organismal checkpoints and develop into cancer. The architecture of the Wnt, TGF-β, and Notch signaling pathways is simple. The transmembrane receptor, activated by the extracellular stimulus, induces nuclear translocation of the transcription factor, which subsequently changes the expression of target genes. Nevertheless, these pathways are regulated by a myriad of factors involved in various feedback mechanisms or crosstalk. The most prominent group of regulators is the ubiquitin-proteasome system (UPS). To open the door to UPS-based therapeutic manipulations, a thorough understanding of these regulations at a molecular level and rigorous confirmation in vivo are required. In this quest, mouse models are exceptional and, thanks to the progress in genetic engineering, also an accessible tool. Here, we reviewed the current understanding of how the UPS regulates the Wnt, TGF-β, and Notch pathways and we summarized the knowledge gained from related mouse models.
- MeSH
- beta-katenin metabolismus MeSH
- buněčná diferenciace fyziologie MeSH
- homeostáza genetika MeSH
- ligasy metabolismus MeSH
- myši embryologie genetika MeSH
- proliferace buněk fyziologie MeSH
- proteiny Wnt metabolismus MeSH
- receptory Notch metabolismus MeSH
- signální dráha Wnt fyziologie MeSH
- transformující růstový faktor beta metabolismus MeSH
- transkripční faktory metabolismus MeSH
- ubikvitin metabolismus MeSH
- ubikvitinligasy metabolismus fyziologie MeSH
- vývojová regulace genové exprese genetika MeSH
- zvířata MeSH
- Check Tag
- myši embryologie genetika MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
Parasite hybrid zones resulting from host secondary contact have never been described in nature although parasite hybridization is well known and secondary contact should affect them similarly to free-living organisms. When host populations are isolated, diverge and recontact, intimate parasites (host specific, direct life cycle) carried during isolation will also meet and so may form parasite hybrid zones. If so, we hypothesize these should be narrower than the host's hybrid zone as shorter parasite generation time allows potentially higher divergence. We investigate multilocus genetics of two parasites across the European house mouse hybrid zone. We find each host taxon harbours its own parasite taxa. These also hybridize: Parasite hybrid zones are significantly narrower than the host's. Here, we show a host hybrid zone is a suture zone for a subset of its parasite community and highlight the potential of such systems as windows on the evolutionary processes of host-parasite interactions and recombinant pathogen emergence.
- MeSH
- fylogeneze MeSH
- genetické markery MeSH
- genotyp MeSH
- hlístice genetika MeSH
- hybridizace genetická * MeSH
- mitochondriální DNA genetika MeSH
- myši genetika parazitologie MeSH
- paraziti genetika MeSH
- Pneumocystis genetika MeSH
- populační genetika * MeSH
- zvířata MeSH
- Check Tag
- myši genetika parazitologie MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Česká republika MeSH
- Německo MeSH
Gut microbiota provides a wide range of beneficial function for the host and has an immense effect on the host's health state. It has also been shown that gut microbiome is often involved in the biotransformation of xenobiotics; however, the molecular mechanisms of the interaction between the gut bacteria and the metabolism of drugs by the host are still unclear. To investigate the effect of microbial colonization on messenger RNA (mRNA) expression of liver cytochromes P450 (CYPs), the main drug-metabolizing enzymes, we used germ-free (GF) mice, lacking the intestinal flora and mice monocolonized by non-pathogenic bacteria Lactobacillus plantarum NIZO2877 or probiotic bacteria Escherichia coli Nissle 1917 compared to specific pathogen-free (SPF) mice. Our results show that the mRNA expression of Cyp1a2 and Cyp2e1 was significantly increased, while the expression of Cyp3a11 mRNA was decreased under GF conditions compared to the SPF mice. The both bacteria L. plantarum NIZO2877 and E. coli Nissle 1917 given to the GF mice decreased the level of Cyp1a2 mRNA and normalized it to the control level. On the other hand, the colonization by these bacteria had no effect on the expression of Cyp3a11 mRNA in the liver of the GF mice (which remained decreased). Surprisingly, monocolonization with chosen bacterial strains has shown a different effect on the expression of Cyp2e1 mRNA in GF mice. Increased level of Cyp2e1 expression observed in the GF mice was found also in mice colonized by L. plantarum NIZO2877; however, the colonization with probiotic E. coli Nissle 1917 caused a decrease in Cyp2e1 expression and partially restored the SPF mice conditions.
- MeSH
- Escherichia coli genetika růst a vývoj metabolismus MeSH
- gnotobiologické modely MeSH
- játra enzymologie MeSH
- Lactobacillus genetika růst a vývoj metabolismus MeSH
- messenger RNA genetika metabolismus MeSH
- myši inbrední BALB C MeSH
- myši genetika mikrobiologie MeSH
- střevní mikroflóra * MeSH
- systém (enzymů) cytochromů P-450 genetika metabolismus MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši genetika mikrobiologie MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Rodents of the genus Mus represent one of the most valuable biological models for biomedical and evolutionary research. Out of the four currently recognized subgenera, Nannomys (African pygmy mice, including the smallest rodents in the world) comprises the only original African lineage. Species of this subgenus became important models for the study of sex determination in mammals and they are also hosts of potentially dangerous pathogens. Nannomys ancestors colonized Africa from Asia at the end of Miocene and Eastern Africa should be considered as the place of their first radiation. In sharp contrast with this fact and despite the biological importance of Nannomys, the specimens from Eastern Africa were obviously under-represented in previous studies and the phylogenetic and distributional patterns were thus incomplete. RESULTS: We performed comprehensive genetic analysis of 657 individuals of Nannomys collected at approximately 300 localities across the whole sub-Saharan Africa. Phylogenetic reconstructions based on mitochondrial (CYTB) and nuclear (IRBP) genes identified five species groups and three monotypic ancestral lineages. We provide evidence for important cryptic diversity and we defined and mapped the distribution of 27 molecular operational taxonomic units (MOTUs) that may correspond to presumable species. Biogeographical reconstructions based on data spanning all of Africa modified the previous evolutionary scenarios. First divergences occurred in Eastern African mountains soon after the colonization of the continent and the remnants of these old divergences still occur there, represented by long basal branches of M. (previously Muriculus) imberbis and two undescribed species from Ethiopia and Malawi. The radiation in drier lowland habitats associated with the decrease of body size is much younger, occurred mainly in a single lineage (called the minutoides group, and especially within the species M. minutoides), and was probably linked to aridification and climatic fluctuations in middle Pliocene/Pleistocene. CONCLUSIONS: We discovered very high cryptic diversity in African pygmy mice making the genus Mus one of the richest genera of African mammals. Our taxon sampling allowed reliable phylogenetic and biogeographic reconstructions that (together with detailed distributional data of individual MOTUs) provide a solid basis for further evolutionary, ecological and epidemiological studies of this important group of rodents.
- MeSH
- biologická evoluce MeSH
- fylogeneze * MeSH
- fylogeografie MeSH
- myši klasifikace genetika MeSH
- zvířata MeSH
- Check Tag
- myši klasifikace genetika MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- subsaharská Afrika MeSH
Výzkum patogeneze chorob a iniciální fáze testování možných, v léčbě využitelných přípravků se neobejde bez preklinických studií. Studium chování buněk obvykle začíná u buněčných kultur. Použít lze buněčné linie – jedná se buď o buňky uměle imortalizované, tj. nesmrtelné, nebo nádorové. Buňky pro primární buněčné kultury jsou získávány buď z tkání zdravých osob, nebo nemocných s příslušnou diagnózou. O něco komplexnější pohled nabízejí myší modely. K vytvoření fibrotické odpovědi v plicní tkáni jsou využívány následující systémy: bleomycinový, využívající FITC, radiační poškození, křemík, transgenní modely, virové vektory a adoptivní transfer lidských fibroblastů do imunodeficitní myši. Recentně vyvinuté modely umožňující pochopení patogeneze a patofyziologie idiopatické plicní fibrózy zahrnují buněčné kokultivace (sledování buněčných interakcí), orgánovou kultivaci nebo tzv. lung slices, tenké plátky nativní plíce kultivované in vitro. Při interpretaci výsledků studií využívajících výše uvedené modely je nutno zohlednit jejich četné limity.
Research into disease pathogenesis and the initial phase of testing compounds to be potentially used in therapy cannot be performed without preclinical studies. The study of cell behavior usually starts with cell cultures. Cell lines may be used; these are either artificially immortalized cells or tumor cells. Cells for primary cell cultures are obtained from tissues of either healthy individuals or patients with a particular diagnosis. I bit more comprehensive view is provided by mouse models. To induce a fibrotic response in the lung tissue, the following systems are used; bleomycin, FITC, radiation injury, sflicon, transgenic models, viral vector and adoptive transfer of human fibroblasts into immunodeficient mice. Recentiy developed models allowing understanding of the pathogenesis and pathophysiology of idiopathic pulmonary fibrosis include cell co-cultures (observation of cell interactions), organ culture or the so-called lung slices, thin slices of the native lung cultured in vitro. When interpreting results of studies using the above models, their numerous limits must be taken into consideration.
- MeSH
- bleomycin MeSH
- geneticky modifikovaná zvířata MeSH
- idiopatická plicní fibróza * etiologie patologie MeSH
- kultivační techniky * metody MeSH
- kultivované buňky MeSH
- lidé MeSH
- modely nemocí na zvířatech * MeSH
- myši genetika MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši genetika MeSH
- zvířata MeSH
- Publikační typ
- práce podpořená grantem MeSH
