The “Rhesus” blood group is well-known from the public for its importance in the field of transfusion medicine.
For several years, researchers from ULB have been studying Rhesus factors. These factors belong to a family comprising five proteins, three of which are present at the red cell surface (RhCE, RhD and RhAG) and determine the Rhesus blood group, and two others (RhBG and RhCG) which are found in various organs including the kidney, the liver and the male genital tract.
The function of Rhesus factors remained completely unknown till Dr. Anna Maria Marini (Research associate from the FNRS) and her collaborators (Laboratory of Molecular Physiology of the Cell, Prof. Bruno André, ULB, IBMM, Charleroi) established a relationship between Rhesus factors and yeast ammonium transporters. Ammonium is used as a major nitrogen source by microbes and plants but is rather known for its toxicity and its implication in the regulation of blood acidity (pH) in mammals.
In 2000, this research group proposes that Rhesus factors play a role in the transport of ammonium in mammals, a process also remaining unknown in animals. This hypothesis was tested by Dr. Sophie Biver during her doctoral thesis performed in the Laboratory of Biology of Development (Profs Josiane and Claude Szpirer, also at IBMM, ULB), in collaboration with the group of Dr. Marini.
The basic idea is simple: to generate mice deprived of the RHCG gene (the one expressed in the kidney) in order to determine if as proposed, these mice would present anomalies related to a defect in ammonium transport, and in particular to a defect in ammonium excretion in the urine. The mice obtained, bearing an invalidation of the RHCG gene and thus deprived of any RhCG protein, appeared viable but their urine contains too low amounts of ammonium, especially if their food is acid, which has for major consequences an altered blood pH which is too acid and a significant loss of weight.
This discovery - which validates the starting assumption – leads to the revision of the concept taught since the 1940th according to which renal ammonium excretion occurs solely by a process of passive diffusion (which does not imply the function of a protein). These mice show the characteristics of human genetic renal pathologies known under the name of distal renal tubular acidosis and whose determinants are not completely known.
Moreover, the researchers observed that invalidated male mice generated litters of reduced size (whereas invalidated females have a normal fertility). This observation is consistent with the fact that the RHCG gene is expressed in the male genital tract where the fluid of the epididymis shows an abnormal pH (it is too acid) in invalidated mice.
These observations have implications in human medicine. They suggest that in man, mutations affecting the RHCG gene could cause some forms of renal pathologies and/or a loss of male fertility. This last suggestion is relevant knowing that certain observations indicate a reduction of the quality of human sperm, in particular in Western populations.
Co-ordinated by the Université libre de Bruxelles- Institut de biologie et de médecine moléculaires, IBMM -, this research was carried out in collaboration with three other teams (Pr. Oliver Devuyst, Université Catholique de Louvain; Pr. C.A. Wagner, Université de Zurich; Dr P. Houillier, Université Pierre et Marie Curie).
- Biver et al. A role for Rhesus factor Rhcg in renal ammonium excretion and male fertility. Nature, Nov 20, 2008; 456 (7220): 339 DOI: 10.1038/nature07518
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