Selective breeding for differences in cholinergic function: sex differences in the genetic regulation of sensitivity to the anticholinesterase, DFP.

Abstract

Genetic factors involved in the sensitivity of behavioral and physiological variables to the anticholinesterase diisopropyl fluorophosphate (DFP) were studied by comparing the sensitivities to DFP of two lines of rats selectively bred to be either sensitive ( Flinders S-line) or resistant ( Flinders R-line) with F1 and F2 genetic crosses between the two lines. The dependent variables selected were body weight, core body temperature, and water intake. Statistical analyses with two-way ANOVA revealed highly significant line differences for all variables and significant sex differences for core body temperature and water intake. Among the lines and crosses the S-line was more sensitive, followed in order by the F2, F1 and R-line. However, the relative differences among the lines varied for the two sexes. The F1 males were almost identical to their R-line counterparts, whereas F1 females were intermediate between the female S- and R-lines. The data were also subjected to discriminant function analyses and similar relationships were found. Estimates of the number of genes involved in the inheritance of DFP sensitivity suggest a single gene in males and two genes in females. The data for the males were reasonably consistent with a model for a single recessive gene coding for DFP sensitivity. On the other hand, the data for the females could be fitted better with a two-gene model, although there was not a complete fit with the observed data. These results provide strong support for sex differences in the genetic regulation of DFP sensitivity.