Confirmation of quantitative trait loci for ethanol sensitivity and neurotensin receptor density in crosses derived from the inbred high and low alcohol sensitive selectively bred rat lines.
BACKGROUND
Genetically influenced alcohol sensitivity is thought to be an important risk factor for the development of alcoholism. An effective first step for identifying genes that mediate variation in alcohol sensitivity is through quantitative trait loci (QTL) mapping in model organisms.


OBJECTIVE
Fourteen provisional QTLs related to alcohol sensitivity were previously mapped in an F2 derived from the IHAS1 and ILAS1 rat lines. The objective of the current study was to confirm those QTLs in an independently derived F2 and in congenics that were bred for two of the loci.


METHODS
IHAS1 X ILAS1 F2 (n=450) were tested for alcohol-induced loss of righting reflex (LORR), blood ethanol concentration at regain of righting reflex (BECRR), sensitivity and acute tolerance on the Rotarod, and neurotensin receptor density (NTR1). Rats were genotyped at the 14 candidate loci and QTL mapping was conducted. Reciprocal congenic strains were bred for loci on chromosomes 2 and 5 and tested for LORR and BECRR.


RESULTS
Four LORR QTLs were mapped at the suggestive or significant level (chromosomes 2, 5, 12, and 13). BECRR was mapped to chromosomes 5, 12, and 13 either in the original or current experiment. Results of the congenic experiment also support QTLs for LORR and BECRR on chromosomes 2 and 5. QTLs for NTR1 density and behavior on the Rotarod were not confirmed.


CONCLUSIONS
QTL mapping in crosses derived from the IHAS1 and ILAS1 has successfully identified loci related to alcohol sensitivity. Recombinant congenics are now being bred to more finely map the confirmed QTLs.
Radcliffe
Richard A
RA
Department of Pharmaceutical Sciences, University of Colorado at Denver and Health Sciences Center, 4200 East Ninth Ave., Denver, CO, 80262, USA. richard.radcliffe@uchsc.edu
Bludeau
Pequita
P
Asperi
William
W
Fay
Tina
T
Deng
X-S
XS
Erwin
V Gene
VG
Deitrich
Richard A
RA
D000437:Alcoholism / Q000235:genetics; D000818:Animals; D001947:Breeding / Q000379:methods*; D002874:Chromosome Mapping / Q000379:methods; D033481:Chromosomes, Mammalian / Q000235:genetics; D000431:Ethanol / Q000008:administration & dosage / Q000633:toxicity*; D005260:Female; D005838:Genotype; D007274:Injections, Intraperitoneal; D008297:Male; D008636:Mesencephalon / Q000187:drug effects / Q000378:metabolism; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D010641:Phenotype; D011699:Putamen / Q000187:drug effects / Q000378:metabolism; D040641:Quantitative Trait Loci / Q000235:genetics*; D051381:Rats; D011919:Rats, Inbred Strains; D018028:Receptors, Neurotensin / Q000235:genetics* / Q000378:metabolism; D012018:Reflex / Q000187:drug effects / Q000235:genetics; D045442:Rotarod Performance Test / Q000379:methods; D012737:Sex Factors; D013997:Time Factors
D018028:Receptors, Neurotensin; C114036:neurotensin type 1 receptor; D000431:Ethanol