title: Female mice heterozygous for creatine transporter deficiency show moderate cognitive deficits.
abstract: Creatine transporter (CrT) deficiency (CTD) is an X-linked disorder characterized by intellectual disability and speech delay. There have been reports that show female carriers have clinical symptoms. We have created CrT knockout (CrT(-/y)) mice in which males show severe cognitive deficits as a model of this disorder. The purpose of this study was to examine if the female carrier mice show cognitive deficits. Reductions in Cr levels as well as CrT transcript were observed in the brains of the female CrT(+/-) mice. CrT(+/-) mice show hyperactivity and increased latency to find the cued platform in the Morris water maze (MWM). CrT(+/-) female mice showed deficits in MWM hidden platform acquisition but not during reversal testing. Memory deficits on probe trials were observed during both phases. Novel object recognition memory and contextual fear memory were not affected in female CrT(+/-) mice. Female CrT(+/-) mice show moderate cognitive deficits, which is consistent with some of the human data. Female CrT(+/-) mice could prove to be beneficial in further understanding CTD and testing therapeutic approaches.
authors.affiliation: Division of Neurology, MLC 7044 Cincinnati Children's Research Foundation, 3333 Burnet Ave., Cincinnati, OH, 45229-3039, USA.
authors.forename: Emily R
authors.initials: ER
authors.lastname: Hautman
authors.forename: Amanda N
authors.initials: AN
authors.lastname: Kokenge
authors.forename: Kenea C
authors.initials: KC
authors.lastname: Udobi
authors.forename: Michael T
authors.initials: MT
authors.lastname: Williams
authors.forename: Charles V
authors.initials: CV
authors.lastname: Vorhees
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Skelton
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D001921:Brain / Q000378:metabolism; D020739:Brain Diseases, Metabolic, Inborn / Q000235:genetics*; D003072:Cognition Disorders / Q000150:complications / Q000235:genetics*; D003401:Creatine / Q000172:deficiency* / Q000235:genetics; D004195:Disease Models, Animal; D005239:Fear; D005260:Female; D005786:Gene Expression Regulation; D006579:Heterozygote; D008124:Locomotion; D018782:Maze Learning; D026901:Membrane Transport Proteins / Q000172:deficiency* / Q000235:genetics*; D008568:Memory; D008569:Memory Disorders / Q000235:genetics; D038901:X-Linked Intellectual Disability / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D050480:Plasma Membrane Neurotransmitter Transport Proteins / Q000172:deficiency* / Q000235:genetics
chemical_list: D026901:Membrane Transport Proteins; D050480:Plasma Membrane Neurotransmitter Transport Proteins; C080679:creatine transporter; D003401:Creatine