title: Modeling partial monosomy for human chromosome 21q11.2-q21.1 reveals haploinsufficient genes influencing behavior and fat deposition.
abstract: Haploinsufficiency of part of human chromosome 21 results in a rare condition known as Monosomy 21. This disease displays a variety of clinical phenotypes, including intellectual disability, craniofacial dysmorphology, skeletal and cardiac abnormalities, and respiratory complications. To search for dosage-sensitive genes involved in this disorder, we used chromosome engineering to generate a mouse model carrying a deletion of the Lipi-Usp25 interval, syntenic with 21q11.2-q21.1 in humans. Haploinsufficiency for the 6 genes in this interval resulted in no gross morphological defects and behavioral analysis performed using an open field test, a test of anxiety, and tests for social interaction were normal in monosomic mice. Monosomic mice did, however, display impaired memory retention compared to control animals. Moreover, when fed a high-fat diet (HFD) monosomic mice exhibited a significant increase in fat mass/fat percentage estimate compared with controls, severe fatty changes in their livers, and thickened subcutaneous fat. Thus, genes within the Lipi-Usp25 interval may participate in memory retention and in the regulation of fat deposition.
authors.affiliation: Wellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdom.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Migdalska
authors.forename: Louise
authors.initials: L
authors.lastname: van der Weyden
authors.forename: Ozama
authors.initials: O
authors.lastname: Ismail
authors.forename: Jacqueline K
authors.initials: JK
authors.lastname: White
authors.forename: Gabriela
authors.initials: G
authors.lastname: Sánchez-Andrade
authors.forename: Darren W
authors.initials: DW
authors.lastname: Logan
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Arends
authors.forename: David J
authors.initials: DJ
authors.lastname: Adams
mesh_terms: D015502:Absorptiometry, Photon; D000818:Animals; D001522:Behavior, Animal; D015139:Blotting, Southern; D002460:Cell Line; D002872:Chromosome Deletion; D002891:Chromosomes, Human, Pair 21 / Q000235:genetics / Q000378:metabolism; D059305:Diet, High-Fat; D005260:Female; D057895:Haploinsufficiency / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D018782:Maze Learning; D051379:Mice; D009006:Monosomy / Q000235:genetics; D021641:Recognition, Psychology; D020133:Reverse Transcriptase Polymerase Chain Reaction