Identification of a locus on mouse chromosome 17 associated with high-affinity choline uptake using BXD recombinant inbred mice and quantitative trait loci analysis.
Using the quantitative trait loci (QTL) approach, preliminary identification has been made of a region on mouse chromosome 17 that influences high-affinity choline uptake (HACU) in the mouse brain. The rate of HACU was measured in synaptosomes prepared from the frontal cortex, hippocampus, and striatum of C57BL/6J (B6), DBA/2J (D2), and 25 BXD recombinant inbred (RI) strains of mice, using a final concentration of 0.5 microM [3H]choline. The strain means of HACU in each area were then correlated with the strain distribution pattern of each of 1300 known genetic markers using a point biserial correlation and 0 (B6 allele) and 1 (D2 allele). Correlations of P < 0.00001 were found between striatal HACU and chromosome 17 markers D17Tu50 and Tcp1. Correlations of P < 0.0001 were found between striatal HACU and chromosome 17 markers D17Leh66e, D17Leh119, D17Rp17e, Plg, D17Leh66d, Ckb-rs2, and Trp53-ps. QTL analyses of HACU in the frontal cortex and hippocampus also revealed correlations with these markers at the level of P < 0.05 and P < 0.01. These data suggest that at least one locus located on mouse chromosome 17 near or between 6 and 13 cM from the centromere influences HACU in the striatum and possibly the frontal cortex and hippocampus of the mouse.
Tarricone
B J
BJ
Department of Psychiatry and Program in Medical Neurobiology, Indiana University School of Medicine, Indianapolis 46202, USA.
Hwang
W G
WG
Hingtgen
J N
JN
Mitchell
S R
SR
Belknap
J K
JK
Nurnberger
J I
JI
D000818:Animals; D001692:Biological Transport; D001921:Brain / Q000378:metabolism*; D002794:Choline / Q000378:metabolism*; D002874:Chromosome Mapping; D003342:Corpus Striatum / Q000378:metabolism; D005260:Female; D005625:Frontal Lobe / Q000378:metabolism; D008040:Genetic Linkage; D005819:Genetic Markers; D006624:Hippocampus / Q000378:metabolism; D008297:Male; D051379:Mice / Q000235:genetics*; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008815:Mice, Inbred Strains; D009474:Neurons / Q000378:metabolism; D011995:Recombination, Genetic
D005819:Genetic Markers; D002794:Choline