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Volume 16, Number 22,
Issue of November 15, 1996
pp. 7193-7205
Copyright ©1996 Society for Neuroscience
Genetic and Environmental Control of Variation in Retinal
Ganglion Cell Number in Mice
Received June 10, 1996; revised Aug. 28, 1996; accepted Sept. 4, 1996.
Robert W. Williams,
Richelle C. Strom,
Dennis S. Rice, and
Dan Goldowitz
Center for Neuroscience, Department of Anatomy and Neurobiology,
University of Tennessee, Memphis, Tennessee 38163
How much of the remarkable variation in neuron number within a
species is generated by genetic differences, and how much is generated
by environmental factors? We address this problem for a single
population of neurons in the mouse CNS. Retinal ganglion cells of
inbred and outbred strains, wild species and subspecies, and
F1 hybrids were studied using an unbiased
electron microscopic method with known technical reliability.
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 genetic factors in a broad sense.
Strain averages have an unanticipated bimodal distribution, with
distinct peaks at 55,500 and 63,500 cells. Three 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 account for a coefficient
of variation that averages ~3.6% within inbred strains and isogenic
F1 hybrids. Age- and sex-related differences in
neuron number are negligible. Variation within isogenic strains appears
to be generated mainly by developmental noise.
Key words:
aging;
brain evolution;
brain weight;
developmental noise;
heritability;
inbred mice;
natural variation;
neuron number;
quantitative trait loci;
retinal ganglion cell;
sex
differences;
wild mice
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