Ssrq1^C57BL/6J
QTL Variant Detail

Summary

• QTL variant: Ssrq1^C57BL/6J
• Name: stress response QTL 1; C57BL/6J
• MGI ID: MGI:3776371
• QTL: Ssrq1 Location: Chr2:142059301-145893953 bp Genetic Position: Chr2, Syntenic

Variant origin

• Strain of Specimen: C57BL/6J

Variant description

• Allele Type: QTL

Notes

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

J:132037

Linkage analysis was performed using 14 AcB (A=A/J; B=C57BL/6J) and 22 BcA recombinant inbred (RI) strains to identify QTLs associated with emotionality and stress response. A panel of 625 polymorphic markers at 2.6 cM resolution was used for genome scan. Approximately 7 animals per strain were evaluated for open field activity and stress response (physical restraint, hypothermia, urinary volume, and urine electrolytes on high-salt diet). Parental strain A/J displays significantly higher emotionality (high anxiety and emergence latencies in the open field and elevated plus maze) compared to parental strain C57BL/6J. Parental strain A/J also displays decreased thermogenesis, urinary volume, and creatinine clearance after stress induced by high-salt diet and physical restraint.

Significant linkage to emotionality in the open field test mapped to mouse Chromosome 1 in the BcA RI strains between D1Mit113 (93.3 cM) and D1Mit356 (95.8 cM) with LOD=4.6. This locus is named Emrq1 (emotional reactivity QTL 1). Potential candidate genes for Emrq1 include Kcnj9 (94.2 cM) and Atp1a2 (94.2 cM). Down-regulation of Atp1a2 was observed in the high-anxiety strain BcA70 compared to C57BL/6J. Bpq2 (81.6 cM) and Emo1 (95 cM) are previously identified QTLs located near Emrq1. Emrq2 (emotional reactivity QTL 2) mapped between D1Mit156 (32.8 cM) and D1Mit435 (36.9 cM) with LOD=3.4 in the AcB RI strains. Emrq2 is linked to emotional reactivity in the elevated plus maze test. Abbp1 (36 cM) and Bpq1 (49.7 cM) are previously identified QTLs located near Emrq2. A potential candidate gene for Emrq2 is Igfbp2 (36.1 cm).

Emotional reactivity mapped to mouse Chromosome 3 in the BcA RI strains between D3Mit216 (58.8 cM) and D3Mit199 (33.7 cM) with LOD=3.9. This locus is named Emrq3 (emotional reactivity QTL 3). Potential candidate genes for Emrq3 include Pitx2 (57.7 cM) and Fabp2 (55 cM). Significant linkage to thermogenesis during stress response mapped near D3Mit224 (22 cM) with LOD=3.3 in AcB RI strains. This locus is named Ssrq3 (stress response QTL 3). Hspa4l is a potential candidate gene for Ssrq3.

Significant linkage to hypothermia during stress response mapped to mouse Chromosome 2 between D2Mit401 (79.7 cM) and D2Mit280 (81.7 cM) with LOD=4. This locus was identified in AcBRI strains and is named Ssrq1 (stress response QTL 1). A/J-derived alleles at Ssrq1 confer increased hypothermic stress response. Insm1 is a potential candidate gene for Ssrq1.

Ssrq2 (stress response QTL 2) mapped to mouse Chromosome 15 between D15Mit175(9.9 cM) and D15Mit115 (24 cM) with LOD=3.9 in AcB RI strains. This locus is linked to hypothermia during stress response. A/J-derived alleles at Ssrq2 confer increased hypothermic stress response. Ptger4 (6.4 cM) is a potential candidate gene for Ssrq2.Previously identified QTL Bpq6 (20.2 cM) maps near Ssrq2.

Ssrq4 (stress response QTL 4) mapped to mouse Chromosome 10 between D10Mit42 (44 cM) and D10Mit231 (52 cM) with LOD=3.5. This locus shows significant linkage to thermogenesis during stress response and was identified in AcB RI strains. Potential candidate genes for Ssrq4 include Cirbp (44 cM) and Igf1 (48 cM).

Significant linkage to high-salt diet and stress-induced hypothermia mapped to mouse Chromosome 4 between D4Mit2 (6.5 cM) and D4Mit361(6.75 cM) with LOD=3.8. This locus was identified in BcA RI strains and is named Ssrq5 (stress response QTL 5). Triglq1 (6.5 cM) is a previously identified QTL mapping near Ssrq5.A second locus on chromosome 4 was identified for high-salt diet induced hypothermic response between D4Mit148 (66 cM) and D4Mit54 (66 cM) with LOD=3.6. This locus is named Ssrq8 (stress response QTL 8). Htr1d (66 cM) is a potential candidate gene for this QTL. A/J-derived alleles at Ssrq5 and Ssrq8 confer increased hypothermic stress response. Significant linkage to urinary calcium secretion after 24 hours on a high-salt diet (LOD=4.1) mapped between D4Mit172 (8.6 cM) and D4Mit89 (19.8 cM) in AcB RI strains. This locus is named Ssrq9 (stress response QTL 9). Npr2 at 21.5 cM is a potential candidate gene for Ssrq9.

The most significant linkage for high-salt dietinduced urinary calcium excretion (LOD=4.6) mapped to mouse Chromosome 12 between D12Mit231 (48 cM) and D12Mit101 (50 cM). This locus was identified in AcB RI strains andisnamed Ssrq6 (stress response QTL 6). Calm1 and Tshr (37 cM) are potential candidate genes for Ssrq6.

Ssrq7 (stress response QTL 7) shows significant linkage to decreased urinary volume after a 24 hour high-salt diet. This locus was identified in BcARI strains and maps to 44.8 cM on mouse Chromosome 11 near D11Mit245 (LOD=3.2). Nos2(45.6 cM) and Myo1c (44.1 cM) are potential candidate genes near Ssrq7.

Ssrq10 (stress response QTL 10) mapped to 20 cM mouse chromosome 18 near D18Mit17 (LOD=3.4). Thislocus is linked to hypothermic response after a high-salt diet and was identified in BcA RI strains. A/J-derived alleles at Ssrq10 confer increased hypothermic response. Nr3c1 at 20 cM is a potential candidate gene for Ssrq10.

Urinary calcium excretion aftera 24-hour high-salt diet shows linkage (LOD=4.1) to a locus between D13Mit77 (73 cM) and D13Mit78 (75 cM). This QTL is named Ssrq11 (stress response QTL 11) and was identified in AcB RI strains. Fgf10 at 75 cM is a potential candidate gene for Ssrq11.

Several other loci associated with high-salt diet-induced urinary calcium excretion mapped to mouse Chromosomes 1 (2 loci), 2, 8, 11, and 17. All linkages were identified in AcB RI strains.

Suggestive loci for emotionality were detected in the BcA RI strains on mouse Chromosomes 4 (between D4Mit181 - D4Mit291 with LOD=3.5, and between D4Mit336 - D4Mit16 with LOD=3.2) and 7 (between D7Mit187 - D7Mit71 with LOD=3.5).

Suggestive linkage to emotional reactivity in the elevated plus maze test mapped to mouseChromosome 7 between D7Mit247 and D7Mit270 (LOD=3.8), mouse Chromosome 9 between D9Mit67 and D9Mit254 (LOD=3.8), mouse Chromosome 11 between D11Mit74 and D11Mit135 (LOD=3.9), and mouse Chromosome 19 at D19Mit10 (LOD=3.9). These loci were identified in the BcA RI strains.

References

• Original: J:132037 Thifault S, et al., Genetic determinants of emotionality and stress response in AcB/BcA recombinant congenic mice and in silico evidence of convergence with cardiovascular candidate genes. Hum Mol Genet. 2008 Feb 1;17(3):331-44
• All: 1 reference(s)