Genetic architecture of the mouse hippocampus: Identification of gene loci with regional effects

L. Lu*, D. C. Airey, and R. W. Williams. Center for Neuroscience, Univ. of Tennessee, Memphis, TN 38163, USA

 

Two quantitative trait loci (QTLs), Hipp1a and Hipp5a, modulate hippocampal size and number of neurons in the dentate gyrus of mouse (Lu et al., 2001, J. Neurosci., vol. 21; www.nervenet.org). Both QTLs act globally and affect many parts of the hippocampus. We now report new QTLs that have restricted effects on specific hippocampal regions. Our biometric analysis is based on reconstructions and unbiased cell counts taken bilaterally from 250 mice that belong to 32 BXD recombinant inbred strains and two parental strains (C57BL/6J and DBA/2J). Material was taken from the Mouse Brain Library (www.mbl.org). Even among strains with the same hippocampal volume, there is substantial residual variation (differences of up to 25%) in the size of hippocampal regions, cell layers, and numbers of neurons. This variation is generated by unknown gene variants. In this study we mapped new QTLs to chromosome (Chr) 6, 13, and 15 (genome-wide P <0.05, R<sup>2</sup> = 0.20.4). HipV15a on Chr 15 controls volume of the hippocampus proper (LRS of 22.6, 2-LOD CI 010 cM). In contrast, DGV13a on Chr 13 controls the volume of the dentate gyrus (LRS of 20.2, 2-LOD CI 2535 cM). GrV6a on Chr 6 controls the volume of the granule cell layer and the total number of granule cells (LRS 16.4, 2-LOD CI 1625 cM). PyV1a on Chr 1 controls the volume of the pyramidal cell layer (LRS 18.3, 2-LOD CI 7080 cM) and overlaps the Hipp1a locus. These new QTLs may colocalize with QTLs and candidate genes that control differences in cell proliferation in hippocampus and perhaps in behavioral capacity. (Our thanks to Dr. Glenn D. Rosen for MBL resource development.)

Key Words: NEUROGENSIS, QUANTITATIVE TRAIT LOCI, NEUROGENETICS, GRANULE CELL

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