RESUMO
The development of gene-targeting technologies has enabled research with immune system-related knockout mouse strains to advance our understanding of how cytokines and their receptors interact and influence a number of body systems, including the central nervous system (CNS). A critical issue when we are interpreting phenotypic data from these knockout strains is the potential role of genes other than the targeted one. Although many of the knockout strains have been made congenic on a C57BL/6 (B6) genetic background, there remains a certain amount of genetic material from the129 substrain that was used in the development of these strains. This genetic material could result in phenotypes incorrectly attributed to the targeted gene. We recently reported low-activity behavior in Il10(-/-) mice that was linked to this genetic material rather than the targeted gene itself. In the current study we confirm the generalizability of those earlier findings, by assessing behavior in Il18(-/-) and Il18r1(-/-) knockout mice. We identified low activity and high anxiety-like behaviors in Il18r1(-/-) mice, whereas Il18(-/-) mice displayed little anxiety-like behavior. Although Il18r1(-/-) mice are considered a congenic strain, we have identified substantial regions of 129P2-derived genetic material not only flanking the ablated Il18r1 on Chromosome 1, but also on Chromosomes 4, 5, 8, 10, and 14. Our studies suggest that residual 129-derived gene(s), rather than the targeted Il18r1 gene, is/are responsible for the low level of activity seen in the Il18r1(-/-) mice. Mapping studies are necessary to identify the gene or genes contributing to the low-activity phenotype.
Assuntos
Ansiedade/genética , Comportamento Exploratório , Subunidade alfa de Receptor de Interleucina-18/deficiência , Subunidade alfa de Receptor de Interleucina-18/genética , Camundongos Congênicos/genética , Atividade Motora/genética , Animais , Ansiedade/psicologia , Mapeamento Cromossômico , DNA/genética , DNA/isolamento & purificação , Modelos Animais de Doenças , Genótipo , Interleucina-18/deficiência , Interleucina-18/genética , Camundongos , Camundongos Congênicos/psicologia , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos , Camundongos Knockout , Fenótipo , Reação em Cadeia da Polimerase , Especificidade da EspécieRESUMO
We review our studies of mate choice with two MHC-congenic strains of mice. This work was stimulated by findings from Yamazaki and colleagues showing that male mice exhibited mate preferences for females whose MHC-haplotype was different from their own, while female mice exhibited either no preference or a weak preference for males of a particular MHC-haplotype (see Beauchamp et al., 1988). Since these findings were unexpected (mate choice theory predicts that females will be more selective than males), we studied the preferences of mice from two additional MHC-congenic strains to assess the generality of the previous findings. Specifically, the goals of our research were: (1) to determine the mate preferences of congenic mice with MHC-haplotypes derived from wild populations, (2) to compare the mate preferences of male and female mice in a test situation where each sex has a clear opportunity to make a choice, and (3) to estimate effects of cross-fostering on each sex.
