Proceedings of The Physiological Society

Europhysiology 2018 (London, UK) (2018) Proc Physiol Soc 41, PCA074

Poster Communications

Genetic ablation of the newly identified androglobin leads to primary ciliary dyskinesia

A. Keppner1, S. Santambrogio2, P. Engeler1, D. Hoogewijs1

1. University of Fribourg, Fribourg, Switzerland. 2. University of Zurich, Zurich, Switzerland.


Globins are small globular metallo-proteins, involved in different cellular functions via their reversible binding capacity to gaseous ligands (O2, CO and NO) and their storage, transport and detoxification (1). Besides the well-established hemoglobin and myoglobin, various new globin types have been discovered in vertebrates, including neuroglobin (2), cytoglobin (3), and more recently also androglobin (Adgb) (4). Adgb is a chimeric protein, consisting of a calpain-like domain and a globin-like domain, and is mainly expressed in testis tissue (4). In this study, we aimed to analyse the in vivo function of Adgb, by investigating Adgb knockout mice. We could observe that knockout animals develop symptoms of primary ciliary dyskinesia (PCD), a genetic disorder that causes abnormal cilia formation and function (5). All knockout male mice display infertility, as a consequence of abnormal sperm flagella formation. Consistently, FACS analysis revealed abnormal elongating spermatids and spermatozoa. Interestingly, we could also demonstrate a strong downregulation of Adgb expression levels in infertile men. Moreover, in roughly 20% of knockouts, we observed development of hydrocephalus within the two first months after birth. We could also notice increased accumulation of mucus in the sinus of these mice. Finally, we encountered few cases of polycystic kidney disease and cardiac hypertrophy. Ongoing electron microscopy analysis of trachea will enable the detection of possible abnormalities of the ciliary structure. Collectively, these results suggest that Adgb represents an essential protein for the formation and/or function of cilia, and that its genetic deletion leads to PCD. Ongoing in vitro approaches should help identifying the underlying molecular mechanisms that link this globin to cilia formation.

Where applicable, experiments conform with Society ethical requirements