Zfp462 deficiency causes anxiety-like behaviors with excessive self-grooming in mice.
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.
Department of Neurology, The Second Affiliated Hospital of Soochow University, Shanghai, China.|Institute for Fetology, The First Affiliated Hospital of Soochow University, Shanghai, China.|Institute of Neuroscience, Soochow University, Shanghai, China.
B
B
Wang
Obstetrics and Gynecology Hospital Research Center, Institute of Reproduction and Development, Fudan University, Shanghai, China.|Institute of Developmental Biology & Molecular Medicine, Fudan University, Shanghai, China.|State Key Laboratory of Genetic Engineering, MOE Key Laboratory of Contemporary Anthropology, and Collaborative Innovation Center for Genetics & Development, School of Life Sciences, Fudan University, Shanghai, China.
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Y
Zheng
Institute of Neuroscience, Soochow University, Shanghai, China.
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H
Shi
Department of Psychiatry, The Affiliated Guangji Hospital of Soochow University, Suzhou City, China.
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Du
Institute for Fetology, The First Affiliated Hospital of Soochow University, Shanghai, China.
Y
Y
Zhang
Institute for Fetology, The First Affiliated Hospital of Soochow University, Shanghai, China.
B
B
Wei
Department of Neurology, The Second Affiliated Hospital of Soochow University, Shanghai, China.
M
M
Luo
Obstetrics and Gynecology Hospital Research Center, Institute of Reproduction and Development, Fudan University, Shanghai, China.|Institute of Developmental Biology & Molecular Medicine, Fudan University, Shanghai, China.|State Key Laboratory of Genetic Engineering, MOE Key Laboratory of Contemporary Anthropology, and Collaborative Innovation Center for Genetics & Development, School of Life Sciences, Fudan University, Shanghai, China.
H
H
Wang
Institute of Developmental Biology & Molecular Medicine, Fudan University, Shanghai, China.|State Key Laboratory of Genetic Engineering, MOE Key Laboratory of Contemporary Anthropology, and Collaborative Innovation Center for Genetics & Development, School of Life Sciences, Fudan University, Shanghai, China.
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Wu
Department of Emergency, Emory University Hospital, Atlanta, GA, USA.
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Hua
Institute for Fetology, The First Affiliated Hospital of Soochow University, Shanghai, China.
M
M
Sun
Department of Neurology, The Second Affiliated Hospital of Soochow University, Shanghai, China.|Institute of Neuroscience, Soochow University, Shanghai, China.
X
X
Xu
D000818:Animals; D001007:Anxiety / Q000378:metabolism*; D001522:Behavior, Animal / Q000502:physiology; D001921:Brain / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism; D004268:DNA-Binding Proteins; D004195:Disease Models, Animal; D006120:Grooming / Q000502:physiology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D009771:Obsessive-Compulsive Disorder / Q000235:genetics / Q000378:metabolism*; D016335:Zinc Fingers
D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D009419:Nerve Tissue Proteins; C519662:Zfp462 protein, mouse
Anxiety disorders; Hoxb8; Pbx1; Zfp462; behavior