Anp32b Deficiency Suppresses Ocular Development by Repression of Pax6

Abstract

Introduction: This study aimed to elucidate the role and molecular mechanisms of acidic leucine-rich nuclear phosphoprotein 32 kDa B (Anp32b) deficiency in ocular development.

Methods: We used constitutive C57BL/6-derived Anp32b-/- mice to elucidate the role of Anp32b in ocular development, including the phenotype and proportion of eye malformation in different genotypes. RNA-seq analysis and rescue experiments were performed to investigate the underlying mechanisms of Anp32b.

Results: Deletion of Anp32b contributes to severe defects in ocular development, including anophthalmia and microphthalmia. Moreover, Anp32b is highly expressed in the lens, and Anp32b-/- embryos with microphthalmia often exhibit severely impaired lens development. Mechanistically, ANP32B directly interacts with paired box protein 6 (PAX6), a master transcriptional regulator, and enhances its transcriptional activity. Overexpression of PAX6 partially but significantly reverses the inhibition of proliferation observed in ANP32B knockdown lens epithelial cells.

Conclusions: Our findings indicate that Anp32b deficiency suppresses ocular development by repressing Pax6 and identify that Anp32b is a viable therapeutic target for ocular developmental defects.

Keywords: Anp32b; Lens development; Lens transcriptome; Ocular malformation; Pax6.