Dataset Information

Quantitative trait loci for interhemispheric commissure development and social behaviors in the BTBR T? tf/J mouse model of autism.

ABSTRACT:

Background

Autism and Agenesis of the Corpus Callosum (AgCC) are interrelated behavioral and anatomic phenotypes whose genetic etiologies are incompletely understood. We used the BTBR T? tf/J (BTBR) strain, exhibiting fully penetrant AgCC, a diminished hippocampal commissure, and abnormal behaviors that may have face validity to autism, to study the genetic basis of these disorders.

Methods

We generated 410 progeny from an F2 intercross between the BTBR and C57BL/6J strains. The progeny were phenotyped for social behaviors (as juveniles and adults) and commisural morphology, and genotyped using 458 markers. Quantitative trait loci (QTL) were identified using genome scans; significant loci were fine-mapped, and the BTBR genome was sequenced and analyzed to identify candidate genes.

Results

Six QTL meeting genome-wide significance for three autism-relevant behaviors in BTBR were identified on chromosomes 1, 3, 9, 10, 12, and X. Four novel QTL for commissural morphology on chromosomes 4, 6, and 12 were also identified. We identified a highly significant QTL (LOD score?=?20.2) for callosal morphology on the distal end of chromosome 4.

Conclusions

We identified several QTL and candidate genes for both autism-relevant traits and commissural morphology in the BTBR mouse. Twenty-nine candidate genes were associated with synaptic activity, axon guidance, and neural development. This is consistent with a role for these processes in modulating white matter tract development and aspects of autism-relevant behaviors in the BTBR mouse. Our findings reveal candidate genes in a mouse model that will inform future human and preclinical studies of autism and AgCC.

SUBMITTER: Jones-Davis DM

PROVIDER: S-EPMC3626795 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Publications

Quantitative trait loci for interhemispheric commissure development and social behaviors in the BTBR T⁺ tf/J mouse model of autism.

Jones-Davis Dorothy M DM Yang Mu M Rider Eric E Osbun Nathan C NC da Gente Gilberto J GJ Li Jiang J Katz Adam M AM Weber Michael D MD Sen Saunak S Crawley Jacqueline J Sherr Elliott H EH

PloS one 20130415 4

<h4>Background</h4>Autism and Agenesis of the Corpus Callosum (AgCC) are interrelated behavioral and anatomic phenotypes whose genetic etiologies are incompletely understood. We used the BTBR T⁺ tf/J (BTBR) strain, exhibiting fully penetrant AgCC, a diminished hippocampal commissure, and abnormal behaviors that may have face validity to autism, to study the genetic basis of these disorders.<h4>Methods</h4>We generated 410 progeny from an F2 intercross between the BTBR and C57BL/6J strains. The p ...[more]

PMID: 23613947

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