title: Monoamine oxidase A and A/B knockout mice display autistic-like features.
abstract: Converging lines of evidence show that a sizable subset of autism-spectrum disorders (ASDs) is characterized by increased blood levels of serotonin (5-hydroxytryptamine, 5-HT), yet the mechanistic link between these two phenomena remains unclear. The enzymatic degradation of brain 5-HT is mainly mediated by monoamine oxidase (MAO)A and, in the absence of this enzyme, by its cognate isoenzyme MAOB. MAOA and A/B knockout (KO) mice display high 5-HT levels, particularly during early developmental stages. Here we show that both mutant lines exhibit numerous behavioural hallmarks of ASDs, such as social and communication impairments, perseverative and stereotypical responses, behavioural inflexibility, as well as subtle tactile and motor deficits. Furthermore, both MAOA and A/B KO mice displayed neuropathological alterations reminiscent of typical ASD features, including reduced thickness of the corpus callosum, increased dendritic arborization of pyramidal neurons in the prefrontal cortex and disrupted microarchitecture of the cerebellum. The severity of repetitive responses and neuropathological aberrances was generally greater in MAOA/B KO animals. These findings suggest that the neurochemical imbalances induced by MAOA deficiency (either by itself or in conjunction with lack of MAOB) may result in an array of abnormalities similar to those observed in ASDs. Thus, MAOA and A/B KO mice may afford valuable models to help elucidate the neurobiological bases of these disorders and related neurodevelopmental problems.
authors: Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, CA 90089, USA.
authors: Marco
authors: M
authors: Bortolato
authors: Sean C
authors: SC
authors: Godar
authors: Loai
authors: L
authors: Alzghoul
authors: Junlin
authors: J
authors: Zhang
authors: Ryan D
authors: RD
authors: Darling
authors: Kimberly L
authors: KL
authors: Simpson
authors: Valentina
authors: V
authors: Bini
authors: Kevin
authors: K
authors: Chen
authors: Cara L
authors: CL
authors: Wellman
authors: Rick C S
authors: RC
authors: Lin
authors: Jean C
authors: JC
authors: Shih
mesh_terms: D000818:Animals; D001321:Autistic Disorder / Q000201:enzymology* / Q000235:genetics; D007398:Interpersonal Relations; D008297:Male; D018782:Maze Learning / Q000502:physiology*; D051379:Mice; D057507:Mice, 129 Strain; D018345:Mice, Knockout; D008995:Monoamine Oxidase / Q000172:deficiency* / Q000235:genetics; D009043:Motor Activity / Q000235:genetics / Q000502:physiology*; D014828:Vocalization, Animal / Q000502:physiology
chemical_list: D008995:Monoamine Oxidase