GENETIC AND ENVIRONMENTAL-CONTROL OF VARIATION IN RETINAL GANGLION-CELL NUMBER IN MICE

How much of the remarkable variation in neuron number within a species is generated by genetic differences, and how much is generated by env ironmental factors? We address this problem for a single population of neurons in the mouse CNS. Retinal ganglion cells of inbred and outbre d strains, wild species and subspecies, and F-1 hybrids were studied u sing an unbiased electron microscopic method with known technical reli ability. Ganglion cell numbers among diverse types of mice are highly variable, ranging from 32,000 to 87,000. The distribution of all cases (n = 252) is close to normal, with a mean of 58,500 and an SD of 7800 . Genetic factors are most important in controlling this variation; 76 % of the variance is heritable and up to 90% is attributable to geneti c factors in a broad sense. Strain averages have an unanticipated bimo dal distribution, with distinct peaks al 55,500 and 63,500 cells. Thre e pairs of closely related strains have ganglion cell populations that differ by >20% (10,000 cells). These findings indicate that different alleles at one or two genes have major effects on normal variation in ganglion cell number. Nongenetic factors are still appreciable and ac count for a coefficient of variation that averages similar to 3.6% wit hin inbred strains and isogenic F-1 hybrids. Age- and sex-related diff erences in neuron number are negligible, Variation within isogenic str ains appears to be generated mainly by developmental noise.