Experiment
26 BXD/Ty (B=C57BL/6, D=DBA/2) recombinant inbred (RI) strains were used to map QTLs associated with cocaine related behavior at 4 different doses of cocaine and QTLs associated with dopamine receptor binding.
QTLs for cocaine related behavior mapped to mouse Chromosomes 1, 2, 3, 4, 5, 6, 11, 12, 15, and 19.
On mouse Chromosome 1, Cocrb1 maps to 41 cM - 52.3 cM (LOD = 3.3 at Chrng-previously Acrg) in association with repeated movements at 30 mg/kg and 45 mg/kg cocaine dosages, and Cocrb2 maps to 74.5cM (LOD = 4.8 at D1Ncvs12) in association with nose pokes (exploratory behavior) at 15 mg/kg dosage.
Cocrb3 maps to mouse Chromosome 2 at 69 cM (LOD = 3.3 at D2Byu3) and is associated with nose pokes at 30 mg/kg dosage.
Cocrb4 maps to mouse Chromosome 3 at 70 cM (LOD = 3.7 at D3Ncvs49) in association with nose pokes at 15 mg/kg cocaine dosage.
Cocrb5 maps to mouse Chromosome 4 at 38.9 cM (LOD = 3.7 at Adfp) in association with repeated movements at 5 mg/kg dosage. Cocrb5 maps near Iapls3-10, Il14, Grik3, Oprd1, and Slc9a1.
Cocrb6 is a female specific locus mapping to 50 cM - 59 cM on mouse Chromosome 5 (LOD = 3.3 at D5Mit7) in association with total distance (15 mg/kg and 45 mg/kg), repeated movements (all doses), and center time (30 mg/kg).
Cocrb7 maps to mouse Chromosome 6 at 26.5 cM (LOD = 3.3 at D6Rik55) in association with repeated movements at 5 mg/kg dosage.
On mouse Chromosome 9, Cocrb8 (female specific) maps to 28 cM - 29 cM (LOD = 3.8 at D9Mit4) in association with repeated movementsat 45 mg/kg, Cocrb9 maps to 42 cM (LOD = 3.0 at D9Ncvs47) in association with slope of activity measures, and Cocrb10 (male specific) maps to 70 cM (LOD = 3.2 at D9Ncvs45) in association with nose pokes at 5 mg/kg dosage. Possible candidate genes for Cocrb9 are Nedd4a and Tcf12.
On mouse Chromosome 11, Cocrb11 maps to 2 cM-11 cM (LOD=4.2 at Glns-ps1) in association with center time at 45 mg/kg, and Cocrb12 (male specific) maps to 74 cM (LOD = 3.1 at D11Ncvs49) in association with nose pokes at 5 mg/kg.Possible candidate genes for Cocrb11 are Ddc and Camk2b.
Cocrb13 maps to 6 cM on mouse Chromosome 12 (LOD = 3.4 at D12Ncvs31) in association with nose pokes at 30 mg/kg dosage.
On mouse Chromosome 15, Cocrb14 (male specific) maps to 39.6 cM (LOD = 3.7 at D15Mit3) in association with total distance at 5 mg/kg, and Cocrb15 maps to 51 cM (LOD = 3.0 at D15Ncvs29) at 30 mg/kg dosage.
Cocrb16 maps to mouse Chromosome 19 at 83 cM (LOD = 3.3 at Tas1r3-previously Sac) in association with repeated movements at 45 mg/kg dosage. *Editor's Note: MGI currently has Tas1r3 positioned on mouse Chromosome 4 at 83 cM*
QTLs for dopamine receptor binding mapped to mouse Chromosomes 1, 5, 7, 9, 11, 12, 15, and 16.
Female specific QTL Dautb1 (dopamine uptake receptorbinding) mapped to 69.9 cM on mouse Chromosome 1 (LOD = 3.8 at D1Ncvs68).
On mouse Chromosome 2, female specific Drb1 (dopamine receptor binding) maps to 7 cM (LOD = 3.5 at D5Ncvs55) and male specific Drb2 maps to 54 cM (LOD = 3.1 at D5Mit10.
Dautb2 maps to mouse Chromosome 7 from 45 cM - 46.2 cM (LOD = 3.5 at Mod-2r).
Female specific Drb3 maps to 61 cM on mouse Chromosome 9 (LOD = 3.6 at D6Rik67).
On mouse Chromosome 11, Dautb3 maps to 25 cM (LOD = 3.6 at D11Ncvs44) and Dautb4 maps to 46 cM (LOD= 3.1 at D11Mit34).
On mouse Chromosome 12, Dbr4 maps to 2 cM (LOD = 3.1 at D12Mit1), female specific Drb5 maps to 25 cM (LOD = 4.8 at Eife4) and male specific Drb6 maps to 59 cM (LOD=3.4 at D12Byu212). Possible candidate genes for Drb6 are Cbg and Ckb.
On mouse chromosome 15, Drb7 maps from 43 cM-47.2 cM (LOD=4.7 at Cyp2d9) and female specific Drb8 maps from 51 cM-53.3 cM (LOD = 4.8 at D15Ncvs23 and D15Ncvs24).
Drb9 maps to 69.1 cM (LOD = 3.1 at D16Byu216) on mouse Chromosome 16.
Authors note regions of dopamine receptor binding and cocaine related behavior QTL colocalization:
Dautb1 and Cocrb2 on mouse Chromosome 1 at 69.9 cM - 74.5 cM
Drb2 and Cocrb6 on mouse Chromosome 5 at 54 cM. Ache, GnB2, and Nos1 are possible candidate genes for Drb2 and/or Cocrb6 on mouse Chromosome 5.
Cocrb13 and Drb4 on mouse Chromosome 12 at 2 cM - 6 cM
Cocrb15, Drb7, and Drb8 on mouse Chromosome 15 at 40 cM - 55 cM. Bzrp, Cacnb, Gpt1 and Scn8a are possible candidate genes for the Chromosome 15 region(s).
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