Abstract
Mice of the strain C3H.PRI-Flvr, carrying genetically determined resistance to flaviviruses, have been shown to be more sensitive to the hypothermic effect of dopamine than congenic flavivirus-susceptible C3H/HeJARC mice. In the current study, the greater sensitivity to dopamine-induced hypothermia observed in flavivirus-resistant mice was shown to be dose-dependent, with strain differences being the most prominent at a moderate dose of apomorphine (1 mg/kg). In addition, hypothermic responses to apomorphine were shown to be under developmental regulation; aging increased the potency of apomorphine-induced hypothermia and abrogated strain and sex differences observed in young mice. Linkage analysis of mouse strain-dependent co-inheritance between flavivirus resistance and greater sensitivity to the hypothermic effect of dopamine was performed using two genetically unrelated flavivirus-susceptible and two highly congenic flavivirus-resistant mouse strains in parallel with C3H.PRI-Flvr-and C3H/HeJARC reference strains. This study has revealed a clear segregation between flavivirus resistance conferred by the Flv locus and sensitivity to dopamine-controlled hypothermia conferred by a novel locus, Diht. Parallel studies in F1 and F2 heterozygote mice showed that the high sensitivity to hypothermic effect of dopamine (Dihthigh) is inherited as the Chr5-linked dominant trait. The novel locus, Diht, has been mapped proximal to the Flv locus on a distal part of mouse Chr5 between microsatellite markers D5Mit41 and D5Mit158.
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Funding for the project was gratefully received from the Western Australian Institute of Medical Research (WAIMR), Australia.
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Stoddart, C.W., Martin–Iverson, M.T., Jablensky, A. et al. A novel mouse Chr5 locus Diht controls dopamine-induced hypothermia. Mamm Genome 15, 901–913 (2004). https://doi.org/10.1007/s00335-004-2394-0
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DOI: https://doi.org/10.1007/s00335-004-2394-0