Dnajb13-flox Mouse

Dnajb13, a type II HSP40 family member, is highly expressed in the testis. It is an axonemal component of mouse mature spermatozoa, localized to the radial spokes of the '9+2' axoneme [3]. DNAJB13 is thought to be involved in the assembly and stability of the axoneme during sperm flagellum development, and may participate in spermiogenesis and the motility of mature spermatozoa [4,5]. It is also expressed in several ciliated cell-containing tissues like the brain, lung, and oviduct [3,4].

In human studies, a novel c.106T>C mutation of DNAJB13 was found in nearly 10% of idiopathic asthenozoospermia patients but absent in fertile men. Sperm from patients with this mutation had tail defects and reduced DNAJB13 protein levels, leading to immotility [1]. A novel homozygous frameshift mutation c.335_336del [p.E112Vfs*3] in DNAJB13 was detected in a primary infertile male patient with abnormal sperm morphology, recurrent respiratory infections, and chronic cough. This mutation negatively affected DNAJB13 expression in spermatozoa, causing ultrastructural defects [2]. Mutations in DNAJB13 also cause primary ciliary dyskinesia (PCD) in humans. In vitro studies showed that a missense substitution (p.Met278Arg) in DNAJB13 led to protein instability and proteasomal degradation, and another mutation (c.68 + 1G>C) resulted in a splicing defect consistent with a loss-of-function mutation [6].

In conclusion, Dnajb13 plays a crucial role in sperm flagellar function, spermiogenesis, and the motility of mature spermatozoa. Mutations in Dnajb13 are associated with male infertility and primary ciliary dyskinesia, highlighting its importance in understanding the genetic basis of these conditions.