Nilac1^A/J
QTL Variant Detail

Summary

• QTL variant: Nilac1^A/J
• Name: nicotine induced locomotor activity 1; A/J
• MGI ID: MGI:3629994
• QTL: Nilac1 Location: Chr11:26011780-26011942 bp Genetic Position: Chr11, cM position of peak correlated region/allele: 15.63 cM
• QTL Note: genome coordinates based on the marker associated with the peak LOD score

Variant origin

• Strain of Specimen: A/J

Variant description

• Allele Type: QTL
• Mutation: Undefined
• This allele confers decreased nicotine-induced locomotor activity compared to C57BL/6J. (J:143889)
• Inheritance: Recessive

Notes

Mapping and Phenotype information for this QTL, its variants and associated markers

J:109827

Linkage analysis was performed on 13 AcB and 22 BcA (A=A/J; B=C57BL/6J) recombinant congenic (RC) strains to identify QTL associated with sensitivity to nicotine-induced locomotor activity. A panel of 625 polymorphic markers at an average resolution of 2.6 cMwas used for the genome scan. Parental strain C57BL/6J is insensitive to nicotine-induced locomotor activity whereas parental strain A/J exhibits reduced activity after nicotine administration. QTL reaching statistical significance of P<0.01 are described below.

In the BcA RC lines, linkage to nicotine-induced locomotor activity mapped to 14 cM at peak marker D11Mit82 and to 49 cM with peak marker D11Mit39 on mouse Chromosome 11. These loci are named Nilac1 (nicotine induced locomotor activity 1) and Nilac2, respectively. The Nilac1 QTL interval spans 1.5 cM to 18 cM. Potential candidate genes near this region are Gabra1 (19 cM) and Gabra6 (23 cM). C57BL/6J-derived alleles at Nilac1 confer increased locomotor activity. The Nilac2 QTL interval spans47.67 cM to 54 cM. Lore4(49 cM) is an ethanol sensitivity QTL mapping near Nilac2. C57BL/6J-derived alleles at Nilac2 confer decreased locomotor activity after nicotine administration.

In the AcB RC lines, Nilac3 (nicotine induced locomotor activity 3) mapped to 83.1 cM on mouse Chromosome 2 with peak marker D2Mit311. The QTL interval spans 71 cM to 96 cM. A/J-derived alleles at Nilac3 confer increased locomotor activity after nicotine administration. Sstr4 at 84 cM is a potential candidate gene for Nilac2.

In the AcB RC lines, Nilac4 (nicotine induced locomotor activity 4) maps to 57.5 cM on mouse Chromosome 7 with peak marker D7Mit66. The QTL interval spans 57.5 to 66.6 cM. A/J-derived alleles at Nilac4 confer increased locomotor activity after nicotine administration.

In the AcB RC lines, Nilac5 (nicotine induced locomotor activity 5) maps to 6 cM on mouse Chromosome 8 with peak marker D8Mit124. A/J-derived alleles at Nilac5 confer increased locomotor activity after nicotine administration.

In the AcB RC lines, linkage to nicotine sensitivity mapped to 16 cM on mouse Chromosome 13 with peak marker D13Mit59. This locus is named Nilac6 (nicotine induced locomotor activity 6). The QTL interval spans 16 cM to 21 cM. A/J-derived alleles at Nilac6 confer increasedlocomotor activity after nicotineadministration. In the BcARC lines, linkage to nicotine sensitivity mapped to 9 cM near D13Mit218. This locus is named Nilac7. The QTL interval spans 8 cM to 11 cM. C57BL/6J-derived alleles at Nilac7 confer increased locomotor activation after nicotine administration.

In the AcBRC lines, Nilac8 (nicotine induced locomotor activity 8) maps to 25 cM on mouse Chromosome 14 with peak marker D14Mit155. A/J-derived alleles at Nilac8 confer increased locomotor activity after nicotine administration.

In the BcA RClines, linkage to nicotine sensitivity mapped to 52 cM with peak marker D14Mit165. This locus is named Nilac9. The QTL interval spans 52 cM to 60 cM. C57BL/6J-derived alleles at Nilac9 confer increased locomotor activityafter nicotine administration.

Inthe AcB RC lines, Nilac10 (nicotine inducedlocomotor activity 10) maps to 4.3 cM on mouse Chromosome 16 to peak marker D16Mit131. The QTL range spans 4.3 cM to 66 cM. A/J-derived alleles at Nilac10 confer increased locomotor activity after nicotine administration.Drd3 at 23.3 cM is a potential candidate gene for Nilac10.

In the BcA RC lines, Nilac11 (nicotine induced locomotor activity 11) maps to 56.7 cM on mouse Chromosome 17 with peak marker D17Mit221.C57BL/6J-derived alleles at Nilac11 confer increased locomotor activity after nicotine administration. Nilac12 was detected in the AcB RC lines and overlaps with Nilac11. This locus peaks at 54.6 cM with marker D17Mit76. The QTL interval spans 44.5 cM to56 cM. A/J-derived alleles at Nilac12 confers increased locomotor activity after nicotine administration.

J:143889

Previously identified QTL associated with sensitivity to nicotine-induced locomotor activity were confirmed using an F2 cross between A/J and C57BL/6J inbred strains and chromosome substitution strains (CSS) carrying A/J-derived donor DNA on a C57BL/6J genetic background. Parental strain C57BL/6J is resistant to nicotine-induced locomotor activity whereas parental strain A/J exhibits reduced activity after nicotine administration. Animals were assessed for locomotor activity in open field boxes for 30 minutes after a single nicotine injection. A population of 351 (A/J x C57BL/6J)F2 animals were phenotyped and approximately 23 animals from each CCS line (except for chromosomes 13 and 19) were phenotyped. Genotype analysis was targeted to regions previously associated with nicotine-induced locomotor QTL.

Nilac1 (nicotine induced locomotor activity 1) was confirmed on mouse Chromosome 11 near D11Mit62. This locus mapped to 1.5 cM in the F2 cross. A/J-derived alleles at Nilac1 confer decreased locomotor activity in response to nicotine administration with recessive inheritance.

On mouse Chromosome 16, Nilac10 (nicotine induced locomotor activity 10) was confirmed in the F2 population with peak linkage at D16Mit131 (4.3 cM). The QTL interval spans 4.3 cM to 21.5 cM between D16Mit131 and D16Mit57. A/J-derived alleles at Nilac10 confer increased locomotor activity after nicotine administration. The effect of this allele appears dominant. A search for candidate genes across the Nilac10 interval revealed nine genes where non-conservative amino acid changes were present between A/J and C57BL/6J strains. Abat was named as a potential candidate for Nilac10 because Abat is expressed in the brain and shows association with behavior phenotypes affected by cocaine and nicotine. Nilac10 was also present in CSS line C57BL/6J-Chr 16^A/J as a female-specific locus. A/J-derived alleles at Nilac10 increased locomotor activation in female C57BL/6J-Chr 16^A/J animals.

CSS line C57BL/6J-Chr 2^A/J confirmed the presence ofNilac3 (83.1 cM). A/J-derived alleles at Nilac3 confer increased locomotor activation after nicotine administration.

Nilac9 (nicotine induced locomotor activity 9) at 52 cM on mouse Chromosome 14 was confirmed in CSS line C57BL/6J-Chr 14^A/J. A/J-derived alleles at Nilac9 confer increased locomotor activation after nicotine administration.

Nilac11 (nicotine induced locomotor activity 11) at 56.7 cM on mouse Chromosome 17 was confirmed in CSS line C57BL/6J-Chr 17^A/J. A/J-derived alleles at Nilac11 confer increased locomotor activity after nicotine administration.

References

• Original: J:109827 Gill KJ, et al., Genetic basis for the psychostimulant effects of nicotine: a quantitative trait locus analysis in AcB/BcA recombinant congenic mice. Genes Brain Behav. 2005 Oct;4(7):401-11
• All: 2 reference(s)