title: Neurobehavioral Alterations in a Genetic Murine Model of Feingold Syndrome 2.
abstract: Feingold syndrome (FS) is an autosomal dominant disorder characterized by microcephaly, short stature, digital anomalies, esophageal/duodenal atresia, facial dysmorphism, and various learning disabilities. Heterozygous deletion of the miR-17-92 cluster is responsible for a subset of FS (Feingold syndrome type 2, FS2), and the developmental abnormalities that characterize this disorder are partially recapitulated in mice that harbor a heterozygous deletion of this cluster (miR-17-92∆/+ mice). Although Feingold patients develop a wide array of learning disabilities, no scientific description of learning/cognitive disabilities, intellectual deficiency, and brain alterations have been described in humans and animal models of FS2. The aim of this study was to draw a behavioral profile, during development and in adulthood, of miR-17-92∆/+ mice, a genetic mouse model of FS2. Moreover, dopamine, norepinephrine and serotonin tissue levels in the medial prefrontal cortex (mpFC), and Hippocampus (Hip) of miR-17-92∆/+ mice were analyzed.Our data showed decreased body growth and reduced vocalization during development. Moreover, selective deficits in spatial ability, social novelty recognition and memory span were evident in adult miR-17-92∆/+ mice compared with healthy controls (WT). Finally, we found altered dopamine as well as serotonin tissue levels, in the mpFC and Hip, respectively, of miR-17-92∆/+ in comparison with WT mice, thus suggesting a possible link between cognitive deficits and altered brain neurotransmission.
authors.affiliation: Dipartimento di Psicologia and Centro "Daniel Bovet", Sapienza - Università di Roma, Rome, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Fiori
authors.forename: L
authors.initials: L
authors.lastname: Babicola
authors.forename: D
authors.initials: D
authors.lastname: Andolina
authors.forename: A
authors.initials: A
authors.lastname: Coassin
authors.forename: T
authors.initials: T
authors.lastname: Pascucci
authors.forename: L
authors.initials: L
authors.lastname: Patella
authors.forename: Y-C
authors.initials: YC
authors.lastname: Han
authors.forename: A
authors.initials: A
authors.lastname: Ventura
authors.forename: R
authors.initials: R
authors.lastname: Ventura
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D001921:Brain / Q000503:physiopathology*; D004195:Disease Models, Animal; D005143:Eyelids / Q000002:abnormalities* / Q000503:physiopathology; D005260:Female; D008607:Intellectual Disability / Q000150:complications / Q000235:genetics / Q000503:physiopathology*; D017880:Limb Deformities, Congenital / Q000150:complications / Q000235:genetics / Q000503:physiopathology*; D008297:Male; D001523:Mental Disorders / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics; D008831:Microcephaly / Q000150:complications / Q000235:genetics / Q000503:physiopathology*; D014138:Tracheoesophageal Fistula / Q000150:complications / Q000235:genetics / Q000503:physiopathology*
chemical_list: C575895:MIRN17-92 microRNA, mouse; D035683:MicroRNAs