Behavioral Abnormalities Observed in Zfhx2-Deficient Mice
نویسندگان
چکیده
Zfhx2 (also known as zfh-5) encodes a transcription factor containing three homeobox domains and 18 Zn-finger motifs. We have reported that Zfhx2 mRNA is expressed mainly in differentiating neurons in the mouse brain and its expression level is negatively regulated by the antisense transcripts of Zfhx2. Although the expression profile of Zfhx2 suggests that ZFHX2 might have a role in a particular step of neuronal differentiation, the specific function of the gene has not been determined. We generated a Zfhx2-deficient mouse line and performed a comprehensive battery of behavioral tests to elucidate the function of ZFHX2. Homozygous Zfhx2-deficient mice showed several behavioral abnormalities, namely, hyperactivity, enhanced depression-like behaviors, and an aberrantly altered anxiety-like phenotype. These behavioral phenotypes suggest that ZFHX2 might play roles in controlling emotional aspects through the function of monoaminergic neurons where ZFHX2 is expressed. Moreover, considering their phenotypes, the Zfhx2-deficient mice may provide a novel model of human psychiatric disorders.
منابع مشابه
HPRT-APRT-deficient mice are not a model for lesch-nyhan syndrome.
Complete hypoxanthine-guanine phosphoribosyl-transferase (HPRT) deficiency in humans results in the Lesch-Nyhan syndrome which is characterized, among other features, by compulsive self-injurious behavior. HPRT-deficient mice generated using mouse embryonic stem cells exhibit none of the behavioral symptoms associated with the Lesch-Nyhan syndrome. Administration of drugs that inhibit adenine p...
متن کاملBehavioral and regulatory abnormalities in mice deficient in the NPAS1 and NPAS3 transcription factors.
Laboratory mice bearing inactivating mutations in the genes encoding the NPAS1 and NPAS3 transcription factors have been shown to exhibit a spectrum of behavioral and neurochemical abnormalities. Behavioral abnormalities included diminished startle response, as measured by prepulse inhibition, and impaired social recognition. NPAS1/NPAS3-deficient mice also exhibited stereotypic darting behavio...
متن کاملA novel human pain insensitivity disorder caused by a point mutation in ZFHX2
Chronic pain is a major global public health issue causing a severe impact on both the quality of life for sufferers and the wider economy. Despite the significant clinical burden, little progress has been made in terms of therapeutic development. A unique approach to identifying new human-validated analgesic drug targets is to study rare families with inherited pain insensitivity. Here we have...
متن کاملDecreased anxiety, altered place learning, and increased CA1 basal excitatory synaptic transmission in mice with conditional ablation of the neural cell adhesion molecule L1.
L1, a neural cell adhesion molecule of the immunoglobulin superfamily, is involved in neuronal migration and differentiation and axon outgrowth and guidance. Mutations in the human and mouse L1 gene result in similarly severe neurological abnormalities. To dissociate the functional roles of L1 in the adult brain from developmental abnormalities, we have generated a mutant in which the L1 gene i...
متن کاملGender Dependent Evaluation of Autism like Behavior in Mice Exposed to Prenatal Zinc Deficiency
Zinc deficiency has recently been linked to the etiology of autism spectrum disorders (ASD) as environmental risk factor. With an estimated 17% of the world population being at risk of zinc deficiency, especially zinc deficiency during pregnancy might be a common occurrence, also in industrialized nations. On molecular level, zinc deficiency has been shown to affect a signaling pathway at gluta...
متن کامل