International Mammalian Genome Society

The 13th International Mouse Genome Conference
October 31-November 3, 1999

Table of Contents * Structure * Bioinformatics * Sequence * Mapping * New Tools * Gene Discovery * Developmental * Mutagenesis * Functional Genomics

E9 Cerebellum-Specific QTLs in the Mouse Brain

David C. Airey, Lu Lu, Richelle Strom, Emmanuel Gilissen, Guomin Zhou, Robert W. Williams. Center for Neuroscience and Department of Anatomy and Neurobiology, Memphis TN 38163

Our aim is to map and characterize genes responsible for quantitative anatomical differences in functional brain systems, with the primary goal of understanding the control of cell number. The cerebellum is an excellent candidate for quantitative genetic dissection because it is a well characterized and discrete part of the CNS that is critical in sensory motor integration and control.

To date we have mapped QTLs influencing cerebellum weight in two sets of recombinant inbred strains, BXD (n = 34 strains, >5 mice/strain) and AXB,BXA (n = 12,12; >5 mice/strain), and two F2 crosses: A/J to BXD5 (n = 447), and C57BL/6J to DBA/2J (n = 183). Here we report our latest results for three QTLs with specific effects on the weight of dissected, fixed cerebellum: Cbm1, Cbm2, and Cbm3. Cerebellar weight scores adjusted by regression for brain weight, body weight, age, sex, and dissector were mapped with Map Manager QT. Cbm1 on Chr 8 has previously been reported by Gilissen and Williams (1997) with 26 BXD strains. We have added data for 8 new BXD strains. Cbm1 retains its genome-wide significance and position in this expanded set with best linkage to D8Mit312 (LRS 17.7 at 40 cM, P < 0.05). No locus with genome-wide significance has yet been mapped with the AXB,BXA dataset, although the highest peak LRS of 12.5 near D4Mit41 is suggestive (genome-wide P < 0.1). Using the ABXD5 F2, Cbm2 was previously reported to map near D19Mit123 with a genome-wide P < 0.001 by Airey et al. (1998) and confirmed using the BXDs (LRS of 8, P point-wise ~0.005 at D19Mit41). Cbm3 was mapped using the B6D2 F2 near the marker D1Mit57 and has an extremely significant genome-wide P < 0.0001 (peak LRS 43.1, LOD = 9.5). The additive effect per D alleles is nearly +2 mg. The Hipp1 locus, a QTL that modulates hippocampal weight in the B6D2 F2, also maps to distal Chr 1 (see L. Lu et al.). However, D alleles at Hipp1 are associated with a smaller hippocampus. Mapping both these QTLs using a 10th generation advanced intercross will allow us to test whether Hipp1 and Cbm3 are closely linked QTLs or a single locus affecting a cell type common to both CNS regions.


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