| First Author | Drapeau E | Year | 2014 |
| Journal | Dis Model Mech | Volume | 7 |
| Issue | 6 | Pages | 667-81 |
| PubMed ID | 24652766 | Mgi Jnum | J:206790 |
| Mgi Id | MGI:5552847 | Doi | 10.1242/dmm.013821 |
| Citation | Drapeau E, et al. (2014) Absence of strong strain effects in behavioral analyses of Shank3-deficient mice. Dis Model Mech 7(6):667-681 |
| abstractText | Haploinsufficiency of SHANK3, caused by chromosomal abnormalities or mutations that disrupt one copy of the gene, leads to a neurodevelopmental syndrome called Phelan-McDermid Syndrome that can include absent or delayed speech, intellectual disability, neurological changes, and autism spectrum disorders. The SHANK3 protein forms a key structural part of the post-synaptic density. We previously generated and characterized mice with a targeted disruption of Shank3 in which exons coding for the ankyrin repeat domain were deleted and expression of full-length Shank3 was disrupted. We documented specific deficits in synaptic function and plasticity, along with reduced reciprocal social interactions in Shank3 heterozygous mice. Changes in phenotype due to a mutation at a single locus are quite frequently modulated by other loci, most dramatically when the entire genetic background is changed. In mice, each strain of laboratory mouse represents a distinct genetic background and alterations in phenotype due to gene knockout or transgenesis are frequently different across strains, which can lead to the identification of important modifier loci. We have investigated the effect of genetic background on phenotypes of Shank3-heterozygous, knock-out and wild-type mice, using C57BL/6, 129SVE, and FVB/Ntac strain backgrounds. We focused on observable behaviors with the goal of carrying out subsequent analyses to identify modifier loci. Surprisingly, there were very modest strain effects over a large battery of analyses. These results indicate that behavioral phenotypes associated with Shank3 haploinsufficiency are largely strain independent. |
