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Published on: July 14, 2016
Genetical differences in sensitivity to tremorine and oxotremorine in mice
Abstract:
Male mice from 14 strains were injected i.p. with tremorine (3.0 mg/kg) or oxotremorine (0.15 or 0.1 mg/kg). Large inter-strain differences in the degree and duration of the subsequent hypothermia were noted. 2 strains, BALB/c and Simpson, were particularly sensitive to the hypothermic effect of oxotremorine. The offspring from a cross between BALB/c and Simpson were less sensitive than the parental strains, suggesting genetic complementation. A set of 7 recombinant inbred (RI) lines derived from strains C57BL and BALB/c were tested with oxotremorine. 5 RI lines resembled strain C57BL in their response and 2 RI lines resembled strain BALB/c. It was concluded that strains C57BL and BALB/c differ at a gene which has a major effect on the response to oxotremorine.
Insights
Genetic differences in mouse strains significantly impact responses to oxotremorine, a drug causing hypothermia. BALB/c and Simpson strains showed high sensitivity, with offspring exhibiting reduced sensitivity, indicating genetic complementation.
Area of Science:
- Pharmacogenetics
- Neuroscience
- Animal Models
Background:
- Tremorine and oxotremorine are cholinergic agents known to induce hypothermia in rodents.
- Inter-strain variability in drug response is a critical factor in preclinical research.
Purpose of the Study:
- To investigate the genetic basis of strain-dependent differences in hypothermia induced by oxotremorine.
- To identify specific mouse strains and genetic loci influencing sensitivity to oxotremorine.
Main Methods:
- Administration of tremorine and oxotremorine to male mice from 14 different strains.
- Assessment of the degree and duration of hypothermia following drug administration.
- Cross-breeding experiments between sensitive strains (BALB/c and Simpson) and analysis of offspring.
- Testing of recombinant inbred (RI) lines derived from C57BL and BALB/c strains with oxotremorine.
Main Results:
- Significant inter-strain variations in the hypothermic effects of oxotremorine were observed.
- BALB/c and Simpson strains exhibited pronounced sensitivity to oxotremorine-induced hypothermia.
- Offspring from BALB/c x Simpson crosses displayed reduced sensitivity, suggesting genetic complementation.
- RI lines derived from C57BL and BALB/c showed differential responses, with 5 lines resembling C57BL and 2 resembling BALB/c.
Conclusions:
- A major gene influencing the response to oxotremorine differentiates the C57BL and BALB/c mouse strains.
- Genetic factors play a crucial role in determining susceptibility to oxotremorine-induced hypothermia.
- This study provides a foundation for further genetic mapping and characterization of genes involved in cholinergic drug responses.
