title: Neuroanatomical phenotypes in a mouse model of the 22q11.2 microdeletion.
abstract: Recurrent deletions at the 22q11.2 locus have been established as a strong genetic risk factor for the development of schizophrenia and cognitive dysfunction. Individuals with 22q11.2 deletions have a range of well-defined volumetric abnormalities in a number of critical brain structures. A mouse model of the 22q11.2 deletion (Df(16)A(+/-)) has previously been utilized to characterize disease-associated abnormalities on synaptic, cellular, neurocircuitry, and behavioral levels. We performed a high-resolution MRI analysis of mutant mice compared with wild-type littermates. Our analysis revealed a striking similarity in the specific volumetric changes of Df(16)A(+/-) mice compared with human 22q11.2 deletion carriers, including in cortico-cerebellar, cortico-striatal and cortico-limbic circuits. In addition, higher resolution magnetic resonance imaging compared with neuroimaging in human subjects allowed the detection of previously unknown subtle local differences. The cerebellar findings in Df(16)A(+/-) mice are particularly instructive as they are localized to specific areas within both the deep cerebellar nuclei and the cerebellar cortex. Our study indicates that the Df(16)A(+/-)mouse model recapitulates most of the hallmark neuroanatomical changes observed in 22q11.2 deletion carriers. Our findings will help guide the design and interpretation of additional complementary studies and thereby advance our understanding of the abnormal brain development underlying the emergence of 22q11.2 deletion-associated psychiatric and cognitive symptoms.
authors.affiliation: Mouse Imaging Centre, Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: J
authors.initials: J
authors.lastname: Ellegood
authors.affiliation: Department of Psychiatry, College of Physicians and Surgeons, Columbia University, New York, New York, USA.
authors.forename: S
authors.initials: S
authors.lastname: Markx
authors.affiliation: Mouse Imaging Centre, Hospital for Sick Children, Toronto, Ontario, Canada.|Department of Medical Biophysics, University of Toronto, Toronto, Ontario Canada.
authors.forename: J P
authors.initials: JP
authors.lastname: Lerch
authors.affiliation: Mouse Imaging Centre, Hospital for Sick Children, Toronto, Ontario, Canada.|Department of Medical Biophysics, University of Toronto, Toronto, Ontario Canada.
authors.forename: P E
authors.initials: PE
authors.lastname: Steadman
authors.affiliation: Department of Psychiatry, Erasmus Medical Center, The Netherlands.
authors.forename: C
authors.initials: C
authors.lastname: Genç
authors.affiliation: Department of Department of Biomedical Engineering, College of Physicians and Surgeons, Columbia University, New York, New York, USA.
authors.forename: F
authors.initials: F
authors.lastname: Provenzano
authors.affiliation: Department of Psychiatry, Erasmus Medical Center, The Netherlands.
authors.forename: S A
authors.initials: SA
authors.lastname: Kushner
authors.affiliation: Mouse Imaging Centre, Hospital for Sick Children, Toronto, Ontario, Canada.|Department of Medical Biophysics, University of Toronto, Toronto, Ontario Canada.
authors.forename: R M
authors.initials: RM
authors.lastname: Henkelman
authors.affiliation: Department of Psychiatry, College of Physicians and Surgeons, Columbia University, New York, New York, USA.
authors.forename: M
authors.initials: M
authors.lastname: Karayiorgou
authors.affiliation: Department of Psychiatry, College of Physicians and Surgeons, Columbia University, New York, New York, USA.
authors.forename: J A
authors.initials: JA
authors.lastname: Gogos
mesh_terms: D000818:Animals; D001921:Brain / Q000473:pathology*; D002872:Chromosome Deletion; D004062:DiGeorge Syndrome / Q000235:genetics* / Q000473:pathology*; D004195:Disease Models, Animal; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010641:Phenotype; D020542:Third Ventricle / Q000473:pathology