biostudies-literatureKretz PFSwiss National Science FoundationAgence Nationale de la RechercheMedical Research CouncilWellcome Trust261https://www.ebi.ac.uk/biostudies/studies/S-EPMC10647150biostudies-literatureUnknown24(1)<h4>Background</h4>Using mouse genetic studies and systematic assessments of brain neuroanatomical phenotypes, we set out to identify which of the 30 genes causes brain defects at the autism-associated 16p11.2 locus.<h4>Results</h4>We show that multiple genes mapping to this region interact to regulate brain anatomy, with female mice exhibiting far fewer brain neuroanatomical phenotypes. In male mice, among the 13 genes associated with neuroanatomical defects (Mvp, Ppp4c, Zg16, Taok2, Slx1b, Maz, Fam57b, Bola2, Tbx6, Qprt, Spn, Hirip3, and Doc2a), Mvp is the top driver implicated in phenotypes pertaining to brain, cortex, hippocampus, ventricles, and corpus callosum sizes. The major vault protein (MVP), the main component of the vault organelle, is a conserved protein found in eukaryotic cGenome biologyDissecting the autism-associated 16p11.2 locus identifies multiple drivers in neuroanatomical phenotypes and unveils a male-specific role for the major vault protein.PMC10647150ANR-18-CE12-0009MR/S037667/1ANR-10-IDEX-0002-02142603S037667/1Kretz PFWagner CMilhau MSelloum MMikhaleva AFischer MCMorella IHerault YYalcin BKannan MHugel SMontillot CYalcin ICollins SCReymond ABrambilla RfalseDissecting the autism-associated 16p11.2 locus identifies multiple drivers in neuroanatomical phenotypes and unveils a male-specific role for the major vault protein.<h4>Background</h4>Using mouse genetic studies and systematic assessments of brain neuroanatomical phenotypes, we set out to identify which of the 30 genes causes brain defects at the autism-associated 16p11.2 locus.<h4>Results</h4>We show that multiple genes mapping to this region interact to regulate brain anatomy, with female mice exhibiting far fewer brain neuroanatomical phenotypes. In male mice, among the 13 genes associated with neuroanatomical defects (Mvp, Ppp4c, Zg16, Taok2, Slx1b, Maz, Fam57b, Bola2, Tbx6, Qprt, Spn, Hirip3, and Doc2a), Mvp is the top driver implicated in phenotypes pertaining to brain, cortex, hippocampus, ventricles, and corpus callosum sizes. The major vault protein (MVP), the main component of the vault organelle, is a conserved protein found in eukaryotic c2023-01-01T00:00:00Z2023 Nov2026-07-14T19:20:56.242Z2024-10-19T11:17:06.124ZS-EPMC106471503796872610.1186/s13059-023-03092-8