Lack of zinc finger protein 521 upregulates dopamine β-hydroxylase expression in the mouse brain, leading to abnormal behavior.

AIM:Previously, we reported that mice deficient in most of the Zfp521 coding region (Zfp521^Δ/Δ mice) displayed abnormal behaviors, including hyperlocomotion and lower anxiety. In this study, we aimed to elucidate the involvement and mechanisms of monoamine variation. MAIN METHODS:First, we compared the levels of dopamine (DA), noradrenaline (NA), and serotonin in the brains of Zfp521^Δ/Δ and Zfp521^+/+ mice using enzyme-linked immunosorbent assay. Next, we elucidated the mechanisms using quantitative PCR and Additionally, we administered inhibitory drug to the mice and performed behavioral tests. KEY FINDINGS:Our results showed that the DA level decreased and the NA level increased in Zfp521^Δ/Δ mice. We found that ZFP521 suppresses the expression of dopamine β-hydroxylase (DBH), which converts DA into NA. We also demonstrated that paired homeodomain transcription factor 2 and early growth response protein-1, which are the transcription factors for Dbh, were involved in the upregulation of Dbh by ZFP521. The administration of nepicastat, a specific inhibitor of DBH, attenuated the abnormal behaviors of Zfp521^Δ/Δ mice. SIGNIFICANCE:These results suggest that the lack of ZFP521 upregulates the expression of DBH, which leads to a decrease in the DA level and an increase in the NA level in the brain, resulting in abnormal behaviors.

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