Zfp462 deficiency causes anxiety‐like behaviors with excessive self‐grooming in mice

Abstract

Zfp462 is a newly identified vertebrate-specific zinc finger protein that contains nearly 2500 amino acids and 23 putative C2H2-type zinc finger domains. So far, the functions of Zfp462 remain unclear. In our study, we showed that Zfp462 is expressed predominantly in the developing brain, especially in the cerebral cortex and hippocampus regions from embryonic day 7.5 to early postnatal stage. By using a piggyBac transposon-generated Zfp462 knockout (KO) mouse model, we found that Zfp462 KO mice exhibited prenatal lethality with normal neural tube patterning, whereas heterozygous (Het) Zfp462 KO (Zfp462 ) mice showed developmental delay with low body weight and brain weight. Behavioral studies showed that Zfp462 mice presented anxiety-like behaviors with excessive self-grooming and hair loss, which were similar to the pathological grooming behaviors in Hoxb8 KO mice. Further analysis of grooming microstructure showed the impairment of grooming patterning in Zfp462 mice. In addition, the mRNA levels of Pbx1 (pre-B-cell leukemia homeobox 1, an interacting protein of Zfp462) and Hoxb8 decreased in the brains of Zfp462 mice, which may be the cause of anxiety-like behaviors. Finally, imipramine, a widely used and effective anti-anxiety medicine, rescued anxiety-like behaviors and excessive self-grooming in Zfp462 mice. In conclusion, Zfp462 deficiency causes anxiety-like behaviors with excessive self-grooming in mice. This provides a novel genetic mouse model for anxiety disorders and a useful tool to determine potential therapeutic targets for anxiety disorders and screen anti-anxiety drugs.

C2H2-Type Zinc Finger Proteins in Brain Development, Neurodevelopmental, and Other Neuropsychiatric Disorders: Systematic Literature-Based Analysis

“…The potential contribution of ZNF519 to the development of lissencephaly is also supported by the evidence that its expression is downregulated in mice with Lis1, Dcx, or Ywhae knockouts, whose gene mutations are causative for lissencephaly in humans (126). Zfp462, a poly-ZNF involved in the pluripotency and differentiation of embryonic stem cells by regulating the expression of Sox2, Oct4, and Nanog TFs in mice (127), modulates the expression of the genes specific to neuronal differentiation (59). It is predominantly expressed in the embryonic cerebral cortex particularly in the ventricular zone and hippocampus (59).…”

“…Zfp462, a poly-ZNF involved in the pluripotency and differentiation of embryonic stem cells by regulating the expression of Sox2, Oct4, and Nanog TFs in mice (127), modulates the expression of the genes specific to neuronal differentiation (59). It is predominantly expressed in the embryonic cerebral cortex particularly in the ventricular zone and hippocampus (59). Homozygotic Zfp462 knockout is lethal in mice, whereas the heterozygotic mice exhibit developmental delay with low brain weight and anxiety-like behavior with excessive self-grooming (59).…”

“…It is predominantly expressed in the embryonic cerebral cortex particularly in the ventricular zone and hippocampus (59). Homozygotic Zfp462 knockout is lethal in mice, whereas the heterozygotic mice exhibit developmental delay with low brain weight and anxiety-like behavior with excessive self-grooming (59). ZNF148 is a poly-ZNF associated with congenital brain structural defects in humans.…”

Fisetin provides antidepressant effects by activating the tropomyosin receptor kinase B signal pathway in mice

“…; Wang et al . ). An assessment of the normality of data was carried out by the Shapiro–Wilk test before the statistical tests.…”

Viral-mediated overexpression of the Myelin Transcription Factor 1 (MyT1) in the dentate gyrus attenuates anxiety- and ethanol-related behaviors in rats

“…As such, identifying the molecular mechanisms common to anxiety and alcohol abuse may prove crucial to successfully treating alcohol dependence. Previous investigations aimed at identifying the neuroadaptations pertinent to this comorbidity have revealed a potential role for brain zinc finger protein dysregulations in both anxiety and alcohol use disorders (Wang et al 2016).…”