Mapping Data

Experiment

• Experiment
  TEXT-QTL
• Chromosome
  2
• Reference
  J:143889 Boyle AE, et al., Genetic analysis of the psychostimulant effects of nicotine in chromosome substitution strains and F2 crosses derived from A/J and C57BL/6J progenitors. Mamm Genome. 2009 Jan;20(1):34-42
• ID
  MGI:3831818

Genes

Gene	Assay Type
Nilac3	visible phenotype

Notes

• Experiment
  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.