A novel mouse Chr5 locus Diht controls dopamine-induced hypothermia.
Mice of the strain C3H.PRI-Flv(r), 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 coinheritance 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-Flv(r)-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 (Dih-thigh) 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.
Stoddart
Chris W
CW
Western Australian Institute for Medical Research and UWA Centre for Medical Research, The University of Western Australia, Monash Avenue, Nedlands, Western Australia 6009, Australia.
Martin-Iverson
Mathew T
MT
Jablensky
Assen
A
Urosevi
Nadezda
N
D000367:Age Factors; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D004298:Dopamine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D007035:Hypothermia / Q000139:chemically induced / Q000378:metabolism*; D007036:Hypothermia, Induced; D008297:Male; D051379:Mice; D018895:Microsatellite Repeats
D001058:Apomorphine; D004298:Dopamine