Dataset Information

Conditional Loss of Arx From the Developing Dorsal Telencephalon Results in Behavioral Phenotypes Resembling Mild Human ARX Mutations.

ABSTRACT: Mutations in the Aristaless-Related Homeobox (ARX) gene cause structural anomalies of the brain, epilepsy, and neurocognitive deficits in children. During forebrain development, Arx is expressed in both pallial and subpallial progenitor cells. We previously demonstrated that elimination of Arx from subpallial-derived cortical interneurons generates an epilepsy phenotype with features overlapping those seen in patients with ARX mutations. In this report, we have selectively removed Arx from pallial progenitor cells that give rise to the cerebral cortical projection neurons. While no discernable seizure activity was recorded, these mice exhibited a peculiar constellation of behaviors. They are less anxious, less social, and more active when compared with their wild-type littermates. The overall cortical thickness was reduced, and the corpus callosum and anterior commissure were hypoplastic, consistent with a perturbation in cortical connectivity. Taken together, these data suggest that some of the structural and behavioral anomalies, common in patients with ARX mutations, are specifically due to alterations in pallial progenitor function. Furthermore, our data demonstrate that some of the neurobehavioral features found in patients with ARX mutations may not be due to on-going seizures, as is often postulated, given that epilepsy was eliminated as a confounding variable in these behavior analyses.

SUBMITTER: Simonet JC

PROVIDER: S-EPMC4537438 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature

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Conditional Loss of Arx From the Developing Dorsal Telencephalon Results in Behavioral Phenotypes Resembling Mild Human ARX Mutations.

Simonet Jacqueline C JC Sunnen C Nicole CN Wu Jue J Golden Jeffrey A JA Marsh Eric D ED

Cerebral cortex (New York, N.Y. : 1991) 20140502 9

Mutations in the Aristaless-Related Homeobox (ARX) gene cause structural anomalies of the brain, epilepsy, and neurocognitive deficits in children. During forebrain development, Arx is expressed in both pallial and subpallial progenitor cells. We previously demonstrated that elimination of Arx from subpallial-derived cortical interneurons generates an epilepsy phenotype with features overlapping those seen in patients with ARX mutations. In this report, we have selectively removed Arx from palli ...[more]

PMID: 24794919

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Project description:BackgroundDeaf and hard-of hearing (DHH) children often experience emotional/behavioral difficulties. The impact of unilateral/mild hearing loss (HL) on children's emotion and behavior are unclear. We aimed to describe emotional/behavioral, health related quality-of-life (HRQoL) and parent psychological distress outcomes of school-age children with unilateral/mild HL, compared to children with moderate to profound HL, and in relation to population norms; and identify predictive factors of emotional/behavioral difficulties.MethodsData of 339 DHH children, 5-12 years, enrolled in the Victorian Childhood Hearing Longitudinal Databank (VicCHILD), which include demographics, early development, medical/audiological characteristics and parent rated questionnaires of emotion/behavior, HRQoL and parental psychological distress collected at various stages of child's life were analyzed. We used Cohen's d to investigate the outcomes by measuring the mean score differences of both groups with published norms and logistic regression to analyze the factors predictive of emotional/behavioral difficulties.ResultsThe proportion of children with unilateral/mild HL and moderate to profound HL who experienced emotional/behavioral difficulties was similar (18.3% vs. 20.6%), with hyperactivity and poor prosocial behavior reported as the predominant symptoms in both groups. Mean emotional/behavioral scores of both groups were comparable and substantially higher than normative population scores. This was also the case for HRQoL and levels of parent distress. Among children with unilateral/mild HL, additional health needs were the strongest predictive factor, demonstrating an approximately 1.7-fold increase in odds of emotional/behavioral difficulties (OR = 1.67; 95% CI 1.29-2.17, p < 0.001) with every additional health need. Early developmental concerns, other than communication milestone and attending mainstream schoolshowed weaker evidence of association.ConclusionChildren with unilateral/mild HL were just as likely as those with moderate to profound HL to experience more emotional/behavioral difficulties, poorer HRQoL and higher parental distress scores compared to population norms. Our findings justify the provision of early intervention, support and medical services for all DHH children to identify those at risk of poorer outcomes.

Dataset Information

Conditional Loss of Arx From the Developing Dorsal Telencephalon Results in Behavioral Phenotypes Resembling Mild Human ARX Mutations.

Publications

Conditional Loss of Arx From the Developing Dorsal Telencephalon Results in Behavioral Phenotypes Resembling Mild Human ARX Mutations.

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