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Quantificaion of Plzf expression in a rat model of hypertension and metabolic syndrome
Slámová, Petra ; Liška, František (advisor) ; Pravenec, Michal (referee)
Multifactorial diseases like hypertension or metabolic syndrome are significant causes of morbidity and mortality. The metabolic syndrome is mostly characterized by resistance to insulin effect, impairment of lipid metabolism and inclination to hypertension and obesity. Essential hypertension which is the part of the metabolic syndrome is widely spread all over the world and presents the main risk factor for coronary diseases, kidney failure, and stroke. Inbred animal models can be used for identification of the genetic component of complex diseases. The most studied model of metabolic syndrome and essential hypertension is the spontaneously hypertensive rat (SHR), which has proven to be a valuable tool for studying the pharmacological and physiological aspects of blood pressure regulation. There has been significant progress during the last decades in genetic mapping of hypertension and other complex traits in rat models, including SHR. Many of these quantitative trait loci - QTLs are involved in pathogenesis of spontaneous hypertension with the effect on the blood pressure variation about 10-20 mmHg. One QTL involved in blood pressure regulation is located on the rat 8th chromosome. This QTL has been confirmed by the congenic strain SHR-Lx. In this strain the 7-gene 788 kb segment of chromosome 8 of SHR...
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Analysis of cognitive functions in recombinant inbred strains of rats produced by crossbreeding of SHR and BN Lx. lines
Hatalová, Hana ; Stuchlík, Aleš (advisor) ; Pravenec, Michal (referee)
This MSc. thesis deals with dissecting the link between memory, genetics, and metabolic syndrome. Memory is a very complex behavioral trait, probably influenced by innumerable factors. For this experiment HXB/BXH rat recombinant inbred lines (n= 30) and their parental strains (n=2) were used to be trained in the hippocampus dependant spatial learning task called Allothetic Active Place Avoidance. Rats were to memorize sector of a rotating circular arena, which they were to avoid, being motivated by receiving an electric shock upon entering the forbidden sector (4 training sessions; shock sector on the North, 1 retrieval session (no shock), and 3 reversal sessions, to-be-avoided sector facing South; each session 20-min long, retrieval 10-min). Control experiments to exclude impact of motor or sensory abnormalities were run in a form of open-field test and beam-walking test. Correlation with metabolic phenotypes was conducted in an online database of known HXB/BXH phenotypes (GeneNetwork.org). The results showed that differences in learning were significant between the groups (p<0.05); correlation analysis indicated no putative link between selected traits related to metabolic syndrome and memory in rats. The genetic analysis showed a suggestive locus on chromosome 20 for a learning parameter, and...
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Positional cloning of the Hybrid sterility 1 gene: fine genetic mapping and evaluation of two candidate genes
Mihola, Ondřej ; Trachtulec, Zdeněk (advisor) ; Munclinger, Pavel (referee) ; Pravenec, Michal (referee)
Summaryofpublications 1. Positionalcloningof the Hybridsterility1 gene:finegenetic mappingand evaluationof twocandidategenes Hybridsteri|iýis one of the mechanismsof speciation.The Hybridsteriliý1 (HsÍí)genewasthefirstmappedmammaliangene.The geneaffectsfertiliýof male hybridsbetweencertainlaboratorystrains(suchas C57Bl/10)and Mus musculus musculusmiceby causinga breakdownof spermatogenesisat thestageof primary spermatocytes.|ntheprocessof positiona|c|oningoftheHsÍígene,Wegenerateda contigof bacterialartificialchromosomes(BACs)and subsequentlya lowcoverage sequenceof the candidateregionof the '12951/SvlmJstrain.New geneticmarkers narroweddown the HsÍíregionfrom 580 to 360 ki|obases.The productsof two genesfromthisregion,TATA-bindingprotein(Ibp)and proteasomesubunitbeta1 (Psmb1\,accumulateduringspermatogenesis.The proteinshave been described previouslyas having conservedC{erminal sequencesand species-specificN- termini.We eva|uatedthe candidacyof thesegenesfor Hsťíby a||e|icsequencing and by real-timereverse-transcriptionPCR of testicularmRNAs.The resultssuggest thatneitherthePsmÓí northe lbp genecausehybridsteri|ity.Thesing|enuc|eotide po|ymorphisms(SNPs)we havefound,was usedfor the hap|oýpeana|ysisof the HsÍíregion.
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Leishmania tropica: immunopathology and genetic control
Sohrabi, Yahya ; Lipoldová, Marie (advisor) ; Pravenec, Michal (referee) ; Sádlová, Jovana (referee)
Leishmaniasis is a neglected tropical disease caused by protozoan parasites of the genus Leishmania and transmitted by female sand flies. The outcome of Leishmania infection depends both on host and pathogen factors. Similarly as L. major, L. tropica very often causes cutaneous leishmaniasis in humans, but in rare occasions can also visceralize and cause systemic disease. Leishmaniasis cause by L. tropica has become a major public health problem in different endemic foci due to recent outbreaks in several urban areas and spread to new regions. The complications of the disease and lack of safe and effective drug and vaccine against the L. tropica infection require considerable attention to studies of the host-L. tropica interaction. Until recently, the research of leishmaniasis caused by L. tropica was limited due to lack of suitable inbred model and difficulties in inducing infection in animals. The aims of the present project were development of a suitable mouse model of the infection caused by L. tropica, and the study of mechanisms of the disease, and also mapping controlling genes/loci. We analysed susceptibility to L. tropica infection using recombinant congenic (RC) CcS/Dem mouse strains. These strains differ greatly in susceptibility to L. major due to random distribution of 12.5% of STS...
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Leishmania tropica: immunopathology and genetic control
Sohrabi, Yahya ; Lipoldová, Marie (advisor) ; Pravenec, Michal (referee) ; Sádlová, Jovana (referee)
Leishmaniasis is a neglected tropical disease caused by protozoan parasites of the genus Leishmania and transmitted by female sand flies. The outcome of Leishmania infection depends both on host and pathogen factors. Similarly as L. major, L. tropica very often causes cutaneous leishmaniasis in humans, but in rare occasions can also visceralize and cause systemic disease. Leishmaniasis cause by L. tropica has become a major public health problem in different endemic foci due to recent outbreaks in several urban areas and spread to new regions. The complications of the disease and lack of safe and effective drug and vaccine against the L. tropica infection require considerable attention to studies of the host-L. tropica interaction. Until recently, the research of leishmaniasis caused by L. tropica was limited due to lack of suitable inbred model and difficulties in inducing infection in animals. The aims of the present project were development of a suitable mouse model of the infection caused by L. tropica, and the study of mechanisms of the disease, and also mapping controlling genes/loci. We analysed susceptibility to L. tropica infection using recombinant congenic (RC) CcS/Dem mouse strains. These strains differ greatly in susceptibility to L. major due to random distribution of 12.5% of STS...
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Genetics and Genomics of Hybrid Sterility
Bhattacharyya, Tanmoy ; Forejt, Jiří (advisor) ; Pravenec, Michal (referee) ; Macholán, Miloš (referee)
Charles University in Prague Faculty of Science Ph.D. study program: Molecular and Cellular Biology, Genetics and Virology Abstract Genetics and genomics of hybrid sterility Mgr. Tanmoy Bhattacharyya Supervisor: Prof. MUDr. Jiří Forejt, DrSc. Praha 2013 Abstract Male-limited hybrid sterility restricts gene flow between the related species, an important pre- requisite of speciation. The F1 hybrid males of PWD/Ph female (Mus m. musculus subspecies) and C57BL/6J or B6 male (Mus m. domesticus) are azoospermic and sterile (PB6F1), while the hybrids from the reciprocal (B6PF1) cross are semi fertile. A disproportionately large effect of the X chromosome (Chr) on hybrid male sterility is a widespread phenomenon accompanying the origin of new species. In the present study, we mapped two phenotypically distinct hybrid sterility loci Hstx1 and Hstx2 to a common 4.7 Mb region on Chr. X. Analysis of meiotic prophase I of PB6F1 sterile males revealed meiotic block at mid-late pachynema and the TUNEL assay showed apoptosis of arrested spermatocytes. In sterile males over 95% of pachytene spermatocytes showed one or more unsynapsed autosomes visualized by anti SYCP1, HORMAD2 and SYCP3 antibodies. The phosphorylated form of H2AFX histone, normally restricted only to XY chromosome containing sex body decorated unsynapsed...
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Analysis of cognitive functions in recombinant inbred strains of rats produced by crossbreeding of SHR and BN Lx. lines
Hatalová, Hana ; Stuchlík, Aleš (advisor) ; Pravenec, Michal (referee)
This MSc. thesis deals with dissecting the link between memory, genetics, and metabolic syndrome. Memory is a very complex behavioral trait, probably influenced by innumerable factors. For this experiment HXB/BXH rat recombinant inbred lines (n= 30) and their parental strains (n=2) were used to be trained in the hippocampus dependant spatial learning task called Allothetic Active Place Avoidance. Rats were to memorize sector of a rotating circular arena, which they were to avoid, being motivated by receiving an electric shock upon entering the forbidden sector (4 training sessions; shock sector on the North, 1 retrieval session (no shock), and 3 reversal sessions, to-be-avoided sector facing South; each session 20-min long, retrieval 10-min). Control experiments to exclude impact of motor or sensory abnormalities were run in a form of open-field test and beam-walking test. Correlation with metabolic phenotypes was conducted in an online database of known HXB/BXH phenotypes (GeneNetwork.org). The results showed that differences in learning were significant between the groups (p<0.05); correlation analysis indicated no putative link between selected traits related to metabolic syndrome and memory in rats. The genetic analysis showed a suggestive locus on chromosome 20 for a learning parameter, and...
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Quantificaion of Plzf expression in a rat model of hypertension and metabolic syndrome
Slámová, Petra ; Liška, František (advisor) ; Pravenec, Michal (referee)
Multifactorial diseases like hypertension or metabolic syndrome are significant causes of morbidity and mortality. The metabolic syndrome is mostly characterized by resistance to insulin effect, impairment of lipid metabolism and inclination to hypertension and obesity. Essential hypertension which is the part of the metabolic syndrome is widely spread all over the world and presents the main risk factor for coronary diseases, kidney failure, and stroke. Inbred animal models can be used for identification of the genetic component of complex diseases. The most studied model of metabolic syndrome and essential hypertension is the spontaneously hypertensive rat (SHR), which has proven to be a valuable tool for studying the pharmacological and physiological aspects of blood pressure regulation. There has been significant progress during the last decades in genetic mapping of hypertension and other complex traits in rat models, including SHR. Many of these quantitative trait loci - QTLs are involved in pathogenesis of spontaneous hypertension with the effect on the blood pressure variation about 10-20 mmHg. One QTL involved in blood pressure regulation is located on the rat 8th chromosome. This QTL has been confirmed by the congenic strain SHR-Lx. In this strain the 7-gene 788 kb segment of chromosome 8 of SHR...
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