A type I DnaJ homolog, DjA1, regulates androgen receptor signaling and spermatogenesis

Abstract

Two type I DnaJ homologs DjA1 (DNAJA1; dj2, HSDJ/hdj-2, rdj1) and DjA2 (DNAJA2; dj3, rdj2) work similarly as a cochaperone of Hsp70s in protein folding and mitochondrial protein import in vitro. To study the in vivo role of DjA1, we generated DjA1-mutant mice. Surprisingly, loss of DjA1 in mice led to severe defects in spermatogenesis that involve aberrant androgen signaling. Transplantation experiments with green fluorescent protein-labeled spermatogonia into DjA1(-/-) mice revealed a primary defect of Sertoli cells in maintaining spermiogenesis at steps 8 and 9. In Sertoli cells of DjA1(-/-) mice, the androgen receptor markedly accumulated with enhanced transcription of several androgen-responsive genes, including Pem and testin. Disruption of Sertoli-germ cell adherens junctions was also evident in DjA1(-/-) mice. Experiments with DjA1(-/-) fibroblasts and primary Sertoli cells indicated aberrant androgen receptor signaling. These results revealed a critical role of DjA1 in spermiogenesis and suggest that DjA1 and DjA2 are not functionally equivalent in vivo.