title: Absence of Prenatal Forebrain Defects in the Dp(16)1Yey/+ Mouse Model of Down Syndrome.
abstract: Studies in humans with Down syndrome (DS) show that alterations in fetal brain development are followed by postnatal deficits in neuronal numbers, synaptic plasticity, and cognitive and motor function. This same progression is replicated in several mouse models of DS. Dp(16)1Yey/+ (hereafter called Dp16) is a recently developed mouse model of DS in which the entire region of mouse chromosome 16 that is homologous to human chromosome 21 has been triplicated. As such, Dp16 mice may more closely reproduce neurodevelopmental changes occurring in humans with DS. Here, we present the first comprehensive cellular and behavioral study of the Dp16 forebrain from embryonic to adult stages. Unexpectedly, our results demonstrate that Dp16 mice do not have prenatal brain defects previously reported in human fetal neocortex and in the developing forebrains of other mouse models, including microcephaly, reduced neurogenesis, and abnormal cell proliferation. Nevertheless, we found impairments in postnatal developmental milestones, fewer inhibitory forebrain neurons, and deficits in motor and cognitive performance in Dp16 mice. Therefore, although this new model does not express prenatal morphological phenotypes associated with DS, abnormalities in the postnatal period appear sufficient to produce significant cognitive deficits in Dp16.
authors.affiliation: Department of Anatomy and Neurobiology, Boston University School of Medicine, Boston, Massachusetts 02118.
authors.forename: Joseph W
authors.initials: JW
authors.lastname: Goodliffe
authors.affiliation: Department of Anatomy and Neurobiology, Boston University School of Medicine, Boston, Massachusetts 02118.
authors.forename: Jose Luis
authors.initials: JL
authors.lastname: Olmos-Serrano
authors.affiliation: Department of Anatomy and Neurobiology, Boston University School of Medicine, Boston, Massachusetts 02118.
authors.forename: Nadine M
authors.identifier: http://orcid.org/0000-0001-9278-4313
authors.initials: NM
authors.lastname: Aziz
authors.affiliation: Center for Health Protection, National Institute for Public Health and the Environment, 3720 BA Bilthoven, Netherlands, and.
authors.forename: Jeroen L A
authors.identifier: http://orcid.org/0000-0002-9188-6358
authors.initials: JL
authors.lastname: Pennings
authors.affiliation: Mother Infant Research Institute, Floating Hospital for Children, Tufts Medical Center, Boston, Massachusetts 02111.
authors.forename: Faycal
authors.initials: F
authors.lastname: Guedj
authors.affiliation: Mother Infant Research Institute, Floating Hospital for Children, Tufts Medical Center, Boston, Massachusetts 02111.
authors.forename: Diana W
authors.identifier: http://orcid.org/0000-0001-9270-5267
authors.initials: DW
authors.lastname: Bianchi
authors.affiliation: Department of Anatomy and Neurobiology, Boston University School of Medicine, Boston, Massachusetts 02118, thaydar@bu.edu.
authors.forename: Tarik F
authors.identifier: http://orcid.org/0000-0001-6772-3076
authors.initials: TF
authors.lastname: Haydar
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000002:abnormalities* / Q000196:embryology / Q000254:growth & development / Q000473:pathology*; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics; D019465:Craniofacial Abnormalities / Q000209:etiology*; D002658:Developmental Disabilities / Q000209:etiology; D004195:Disease Models, Animal; D004314:Down Syndrome / Q000150:complications* / Q000235:genetics*; D004622:Embryo, Mammalian; D005106:Exploratory Behavior / Q000502:physiology; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D053580:Muscle Strength / Q000235:genetics; D064231:Nestin / Q000235:genetics / Q000378:metabolism; D055495:Neurogenesis / Q000235:genetics; D065852:Spatial Memory / Q000502:physiology; D014314:Trisomy / Q000235:genetics / Q000503:physiopathology*
chemical_list: D064231:Nestin
keywords: cognition; developmental milestones; embryonic development; trisomy 21