DNAH11

This gene encodes a member of the dynein heavy chain family, DNAH11, a microtubule-dependent motor ATPase protein critical for processes involving ciliary movement. The gene DNAH11 has reported associations in a number of important physiological processes including the movement of respiratory cilia, sperm motility, and establishment of the adult body plan.^{[7][10][11][12]} A knockout model of this gene has not been reported.

The body plan is naturally asymmetrical, and the overall order is defined during embryonic gastrulation in mammals where the three germ layers (endoderm, mesoderm, and ectoderm) are established. At the beginnings of gastrulation, the primitive node serves as the organizer and has motile cilia on its surface.^[13][14] These cilia are responsible for directing increased amounts of nodal to the left side of the developing embryo, establishing asymmetry.^[7] For this reason, proper expression of DNAH11 is critical for correct establishment and subsequent development of the asymmetrical body plan.

Mutations in this DNAH11 have been implicated in causing Primary Ciliary Dyskinesia (PCD), formerly called 'immotile cilia syndrome', and results from abnormally motile or static cilia within the respiratory tract.^[7] PCD is characterized by bronchiectasis, frequent upper respiratory tract infections, and issues with fertility, and PCD individuals have increased rates of heterotaxy and situs inversus in approximately 50% of reported cases, a congenital condition in which some organs are mirrored to an abnormal side of the body cavity.^[15][16] Mutations in DNAH11 are also associated with Kartagener syndrome (PCD with situs inversus totalis, a congenital condition with a characteristic total inversion of the body plan and organs).^[15]

Genetic errors with DNAH11 have been shown to cause a number of fertility-related effects in both sexes. Decreased motile cilia-specific expression of DNAH11 within the axoneme of sperm is associated with lower levels of sperm motility.^[17][18] For this reason, males with PCD are not sterile, but they are often infertile under conventional methods due to lack of sperm motility;^[6][18] however, there are cases of DNAH11 mutant males fathering offspring without intervention of assisted reproductive technologies.^[19][20] In females with PCD or Kartagener's syndrome, there are increased reports of subfertility and risk of ectopic pregnancy.^[21][22] Because females' fallopian tubes are lined with motile cilia which show identical motor protein composition to those observed in the respiratory tract, this is believed to result in the increased risks observed in case studies (although affected PCD females' cilia have not been directly analyzed so this remains inconclusive).^[23]