Aubm5^C57BL/6J
QTL Variant Detail

Summary

• QTL variant: Aubm5^C57BL/6J
• Name: autism behavior model 5, juvenile nose to nose sniff; C57BL/6J
• MGI ID: MGI:5807251
• QTL: Aubm5 Location: unknown Genetic Position: Chr9, 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:200109

The BTBR strain provides a unique preclinical rodent model for both autism and Agenesis of the Corps Callosum (AgCC).

The BTBR T⁺Itp3^tf/J (BTBR) inbred mouse strain exhibits deficits in behaviors that may have face validity for the three main diagnostic criteria for autism: impaired social interactions, impairments in communication and repetitive behaviors with restricted interests. The strain is also distinguished by the absence of a corpus callosum, a smaller to absent hippocampal commissure, and a normal to enlarged anterior commissure similar to anatomic changes observed in patients with AgCC.

To investigate the molecular determinants of autism relevant behaviors and commissure development BTBR mice were reciprocally crossed with C57BL/6J mice, which exhibit normal social behaviors with fully formed forebrain commissures. The progeny from 410 (BTBR x C57BL/6J)F2 mice were phenotyped for both juvenile and adult social behaviors as well as commissural morphology and then linkage analysis was performed. Genome wide statistical significance was determined using 1000 permutations. A LOD was considered significant when p<0.05; markers were spaced approximately 10 cM apart and a LOD threshold of 3.39 was declared significant. Following the fine mapping, QTL meeting genome-wide significance of 5% were further analyzed to identify a list of gene candidates for further study.

Seven QTL for four autism relevent behavioral traits, exceeding the 5% genome-wide permutation threshold, were identified. [Fig 4, Table 1]. Six significant QTL were were also identified for commissural morphology. [Fig 5, Table 1].

QTL Aubm1, autism behavior model 1, novel conspecific sniff, was a measure of time spent sniffing a novel mouse in the adult social approach task. Aubm1 mapped to mouse Chromosome 3 with a peak at 18,932,880 bp with a LOD score of 4.52. The confidence interval spanned between 5,370,727 and 32,421,916 bp with a p value of 0.00397 and accounted for 8.6% of trait variance. Table 2 notes that gene Cyp7b1 has previously been implicated in autism spectrum disorders (ASD).

QTL Aubm2, autism behavior model 2, novel conspecific sniff, mapped to Chromosome X; Aubm2 was also as a measure of time spent sniffing a novel mouse in the adult social approach task. Aubm2 peaked at 61,160,361 bp with a LOD score of 4.12 and a p valuce of 0.01190 in a confidence interval that spanned between 45,996,141 and 132,120,932 bp. Table 2 lists Vmn2r121 and Olfr1320 as candidate genes for this QTL.

QTL Aubm3, autism behavior model 3, sniff time difference was a measure of the difference between the time spent sniffing a novel mouse and a novel object. Aubm3 also mapped to mouse Chromosome 3. It peaked at 18,091,440 bp with a LOD score of 4.21. The confidence interval spanned between 5,370,727 and 32,421,916 bp with a p value of 0.0109 and accounted for 8.0% of trait variance.

QTL Aubm4, autism behavior model 4, juvenile nose to nose sniff, was a measure of juvenile social interaction where nose to nose sniffing and the sniffing of the nose and snout region of the partner, were meaasured. Aubm4 QTL mapped to mouse Chromosome 1 with a peak at 174,420,463 bp with a LOD score of 4.43. The confidence interval spanned between 157,761,451 and 193,462,277 bp with a p value of 0.0109 and accounted for 6.8% of trait varaince. Table 2 lists several candidate genes for this QTL including Pappa2 and Prdx2.

A second QTL, Aubm5, autism behavior model 5, juvenile nose to nose sniff, mapped to mouse Chromosome 9 with a peak between 35,057,843 and 44,008,819 bp and a LOD score of 3.80. The confidence interval spanned between 25,697,557 and 120,065,853 bp with a p value of 0.0347. Multiple candidate genes are also listed in Table 2 for this QTL including Olfr160 and Olfr887. Aubm5 was noted as trangressive (e.g. the B6 allele was associated with a decrease in nose to nose sniff time).

QTL Aubm6, autism behavior model 6, juvenile push crawl, was a measure of juvenile social interaction described as push/crawl where the measure was of pushing the head underneath the partner's body or squeezing between the wall/floor and the partner, and crawling over or under the partner's body, combined as a single parameter. Aubm6 mapped to mouse Chromosome 10 with a peak at 101,426,263 bp with a LOD score of 4.77. The confidence interval spanned between 75,175,591 and 113,178,567 bp with a p value of 0.00298 and accounted for 10.3% of trait variance. Table 2 lists Apaf1, Ankrd24, BC030307 and Vezt as candidate genes for this locus.

A second QTL, Aubm7, autism behavior model 7, juvenile push crawl, mapped to mouse Chromosome 12 with a peak between 35,057,843 and 44,008,819 bp and a LOD socre of 4.09. The confidence interval spanned between 53,91,049 and 98,047,413 bp with a p value of 0.01687. Table 2 lists Nkx2-9 and 1110034A24Rik as candidate genes and notes that gene Syne2 has previously been implicated in ASD.

QTL Cmccl1, commissural morphology, corpus callosum lenght 1, mapped to Chromosome 4 peaking at 147,487,273 bp with a LOD score of 20.21 and a p value of less than 0.0001. The confidence interval spanned between 131,622,455 and 155,284,926 bp. Cmccl1 accounted for 15.4% of trait variance. Table 2 lists several candidate loci for this QTL including Luzp1 and 2610109H07Rik.

QTL Cmcca1, commissural morphology, corpus callosum area 1 also mapped to Chromosome 4. Cmcca1 peaked between 131,622,455 and 140,401,003 bp with a LOD score of 10.9 and a p value of less than 0.001. The confidence interval spanned between 122,811,425 and 147,768,403 bp and accounted for 10.5% of trait variance. Several loci are also listed for this QTL in Table 2, including Thrap3 and Dcdc2b.

QTL Cmhcl1, commissural morphology, hippocampal commissure lenght 1, mapped to Chromosome 4 also peaking between 131,622,455 and 140,401,003 bp in a confidence interval spanning between 122,811,425 and 147,768,403 bp. Cmhcl1 had a LOD score of 5.27, a p value of less than 0.001 and accounted for 14.1% of trait variance. Several loci are also listed for this QTL in Table 2, including Thrap3 and Dcdc2b.

QTL Cmchl2, commissural morphology, hippocampal commissure lenght 2, mapped to Chromosome 6, peaking at 103,254,671 bp with a LOD score of 5.36 and a p value of less than 0.001. The confidence interval spanned between 92,537,118 and 111,982,681 bp. Lomd3 is listed in Table 2 as a candidate gene for Cmchl2.

QTL Cmaca1, commissural morphology, anterior commissure area 1, mapped to Chromosome 4 with a peak at 145,114,432 bp and a LOD score of 4.48, a p value of 0.006944 and accounted for 13.1% of trait variance. The confidence interval spanned between 131,622,455 and 155,284,926 bp. Table 2 lists several candidate loci for this QTL including Luzp1 and 2610109H07Rik.

QTL Cmaca2, commissural morphology, anterior commissure area 2, mapped to Chromosome 12 with a peak at 30,474,821 bp and a LOD score of 6.11, a p value of 0.000992. The confidence interval spanned 5,967,934 and 43,749,565 bp. Greb1 and Sox11 are listed in Table 2 as candidate genes for Cmaca2.

References

• Original: J:200109 Jones-Davis DM, et al., Quantitative trait loci for interhemispheric commissure development and social behaviors in the BTBR T(+) tf/J mouse model of autism. PLoS One. 2013;8(4):e61829
• All: 1 reference(s)