Effects of inflammation and diet on the metabolic profile and selected genetic parameters of Bl6 and 129Sv mouse lines
Kuupäev
2023-04-03
Autorid
Ajakirja pealkiri
Ajakirja ISSN
Köite pealkiri
Kirjastaja
Abstrakt
Hiirte geneetiline ülesehitus ühtib suuresti inimesega ning seetõttu on nad asendamatud mudelorganismid nii ravimitööstuses kui ka meditsiinilistes alusteadustes. Hiiri kasutatakse laialdaselt inimeste haiguste modelleerimiseks, et mõista haiguste algpõhjusi ja olemust. Kuid ka ravimite väljatöötamisel nende efektiivsuse ja ohutuse hindamisel. Teaduslaborites kasutatavates hiireliinides on alleelid reeglina homosügootses olekus. Selline geneetiline homogeensus vähendab tulemuste varieeruvust ja hõlbustab uuringute läbiviimist. Samas põhjustab see ka igale hiireliinile unikaalse fenotüübi tekke, mis mõjutab katsetulemusi. Eksperimentide planeerimisel on oluline valida katse eesmärkide jaoks sobilik hiireliin ning sellest lähtuvalt on oluline põhjalikult kaardistada hiireliinide funktsionaalseid erinevusi. Käesoleva doktoritöö eesmärk oli võrrelda kahte hiireliini, Bl6 ja 129Sv, pöörates erilist tähelepanu põletikule ja metaboolse sündroomi tekkele. Meie tulemused näitavad, et Bl6 hiired tulevad paremini toime nii põletiku kui kõrge rasvasisaldusega dieedi põhjustatud negatiivsete mõjudega. Seevastu 129Sv hiired on tundlikumad immuunaktivatsioonile ning suurema vastuvõtlikkusega metaboolse sündroomi tekkele, mis on mõlemad psühhiaatriliste häirete olulised tunnused. Kokkuvõttes võib väita, et Bl6 hiired sobivad paremini agressiivsuse ja sõltuvuskäitumise uurimiseks, seevastu 129Sv hiired sobivad paremini raskemate psühhiaatriliste häiretega seotud endofenotüüpide modelleerimiseks.
The genetic makeup of mice largely corresponds to that of humans, which is why they are irreplaceable model organisms in both the pharmaceutical industry and biomedical research. Mice are often used as model organisms for human diseases to understand the causes and nature of disease. But they are also used in drug development for efficacy and safety testing. Mouse lines used in research laboratories are genetically homogeneous. Such genetic homogeneity reduces variability of results and facilitates experimentation. However, different inbred lines carry different fixed alleles and therefore exhibit different phenotypic characteristics, which affects experimental results. Choosing the right inbred strain for a particular experiment is an important consideration when working with laboratory mice and thus it is important to thoroughly map the functional differences between mouse lines. In this dissertation, two mouse lines, Bl6 and 129Sv, were compared with particular emphasis on inflammation and metabolic syndrome. Our results show that Bl6 mice are better able to cope with the negative effects of inflammation and a high-fat diet. In contrast, 129Sv mice are more sensitive to immune activation and more susceptible to metabolic syndrome, both important features of psychiatric disorders. In summary, Bl6 mice are better suited for studying aggressiveness and addictive behaviors, whereas 129Sv mice are better suited for modeling endophenotypes associated with more severe psychiatric disorders.
The genetic makeup of mice largely corresponds to that of humans, which is why they are irreplaceable model organisms in both the pharmaceutical industry and biomedical research. Mice are often used as model organisms for human diseases to understand the causes and nature of disease. But they are also used in drug development for efficacy and safety testing. Mouse lines used in research laboratories are genetically homogeneous. Such genetic homogeneity reduces variability of results and facilitates experimentation. However, different inbred lines carry different fixed alleles and therefore exhibit different phenotypic characteristics, which affects experimental results. Choosing the right inbred strain for a particular experiment is an important consideration when working with laboratory mice and thus it is important to thoroughly map the functional differences between mouse lines. In this dissertation, two mouse lines, Bl6 and 129Sv, were compared with particular emphasis on inflammation and metabolic syndrome. Our results show that Bl6 mice are better able to cope with the negative effects of inflammation and a high-fat diet. In contrast, 129Sv mice are more sensitive to immune activation and more susceptible to metabolic syndrome, both important features of psychiatric disorders. In summary, Bl6 mice are better suited for studying aggressiveness and addictive behaviors, whereas 129Sv mice are better suited for modeling endophenotypes associated with more severe psychiatric disorders.
Kirjeldus
Väitekirja elektrooniline versioon ei sisalda publikatsioone
Märksõnad
inflammation, diet, transgenic animals, animal models, metabolites, metabolomics