title: Dosage of the Abcg1-U2af1 region modifies locomotor and cognitive deficits observed in the Tc1 mouse model of Down syndrome.
abstract: Down syndrome (DS) results from one extra copy of human chromosome 21 and leads to several alterations including intellectual disabilities and locomotor defects. The transchromosomic Tc1 mouse model carrying an extra freely-segregating copy of human chromosome 21 was developed to better characterize the relation between genotype and phenotype in DS. The Tc1 mouse exhibits several locomotor and cognitive deficits related to DS. In this report we analyzed the contribution of the genetic dosage of 13 conserved mouse genes located between Abcg1 and U2af1, in the telomeric part of Hsa21. We used the Ms2Yah model carrying a deletion of the corresponding interval in the mouse genome to rescue gene dosage in the Tc1/Ms2Yah compound mice to determine how the different behavioral phenotypes are affected. We detected subtle changes with the Tc1/Ms2Yah mice performing better than the Tc1 individuals in the reversal paradigm of the Morris water maze. We also found that Tc1/Ms2Yah compound mutants performed better in the rotarod than the Tc1 mice. This data support the impact of genes from the Abcg1-U2af1 region as modifiers of Tc1-dependent memory and locomotor phenotypes. Our results emphasize the complex interactions between triplicated genes inducing DS features.
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire, Illkirch, 1 rue Laurent Fries, 67404 Illkirch, France; Centre National de la Recherche Scientifique, UMR7104, Illkirch, France; Institut National de la Santé et de la Recherche Médicale, U964, Illkirch, France; Université de Strasbourg, Illkirch, France.
authors.forename: Damien
authors.initials: D
authors.lastname: Marechal
authors.affiliation: Transgenese et Archivage Animaux Modèles, TAAM, CNRS, UPS44, 3B rue de la Férollerie 45071 Orléans, France.
authors.forename: Patricia
authors.initials: P
authors.lastname: Lopes Pereira
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire, Illkirch, 1 rue Laurent Fries, 67404 Illkirch, France; Centre National de la Recherche Scientifique, UMR7104, Illkirch, France; Institut National de la Santé et de la Recherche Médicale, U964, Illkirch, France; Université de Strasbourg, Illkirch, France.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Duchon
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire, Illkirch, 1 rue Laurent Fries, 67404 Illkirch, France; Centre National de la Recherche Scientifique, UMR7104, Illkirch, France; Institut National de la Santé et de la Recherche Médicale, U964, Illkirch, France; Université de Strasbourg, Illkirch, France; Institut Clinique de la Souris, ICS, 1 rue Laurent Fries, 67404 Illkirch, France.
authors.forename: Yann
authors.initials: Y
authors.lastname: Herault
mesh_terms: D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000818:Animals; D033481:Chromosomes, Mammalian; D003071:Cognition / Q000502:physiology; D003072:Cognition Disorders / Q000235:genetics*; D004195:Disease Models, Animal; D004314:Down Syndrome / Q000235:genetics*; D020233:Gait Disorders, Neurologic / Q000235:genetics*; D018628:Gene Dosage; D005838:Genotype; D008074:Lipoproteins / Q000235:genetics*; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D009043:Motor Activity / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D010641:Phenotype; D012193:Reversal Learning / Q000502:physiology; D012261:Ribonucleoproteins / Q000235:genetics*; D045442:Rotarod Performance Test; D000072668:Splicing Factor U2AF; D016615:Telomere
chemical_list: C487540:ABCG1 protein, mouse; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters; D008074:Lipoproteins; D009687:Nuclear Proteins; D012261:Ribonucleoproteins; D000072668:Splicing Factor U2AF; C000607494:U2AF2 protein, human; C000607495:Zrsr1 protein, mouse