As part of the National Research Foundation’s two-year bilateral agreement funding platform, the National Zoological Gardens of South Africa (NZG) and the Cheetah Conservation Fund (CCF, Namibia) have teamed up to investigate the pathology and potential genetic basis of oxalate nephrosis in cheetah. CCF (www.cheetah.org) is the world’s leading organization dedicated to saving the cheetah in the wild and maintains a research program on the biology, ecology and genetics of cheetahs.To compliment, the NZG (www.nzg.ac.za) has a well-established and renowned Research department that undertakes strategic, innovative and interdisciplinary research to contribute to viable wildlife populations within the biodiversity conservation landscape.
What is oxalate nephrosis?
Oxalate nephrosis is a rare renal disease, damaging the kidneys through oxalate crystal deposits, which can be fatal if left untreated. In humans and domestic cats it has been shown to result from mutations in the alanine:glyoxylate aminotransferase (AGT) gene or in the glyoxylate reductase/hydroxypyruvate reductase (GRHPR) gene. The same disease appearance has been identified in the cheetah. An increasing incidence of oxalate nephrosis in captive cheetahs has been documented in the United States, Europe, South Africa, and the United Arab Emirates has led to heightened concern amongst scientists and conservationists. While many other kidney diseases in cheetah are not treatable, oxalate nephrosis may be and identifying the cause of oxalate nephrosis will therefore improve captive cheetah health and welfare.
The pathologists of the NZG as well as CCF collaborator Dr Karen Terio (University of Illinois) have characterized the pathology of the disease in the cheetah. There are multiple potential causes to oxalate nephrosis, but to date factors such as anti-freeze (ethylene glycol) poisoning have been rejected. On the other hand CCF’s investigation of the inheritance of the disease showed that the degree of relatedness between affected individuals is greater than that of the general captive cheetah population. This suggests that the disease has a transmissible component in cheetah.
Tackling the problem head-on…
This collaborative project aims to investigate whether the oxalate nephrosis in the cheetah is caused by mutations in the same genes as in humans and cats. For this the coding regions of both the GRHPR and AGT genes are currently being sequenced in a subset of samples from sick (cases) and healthy (controls) cheetahs. If a mutation is found and appears to be associated with the disease, a specific diagnostic test will be developed. This test would allow screening for this mutation in all captive cheetahs, to facilitate early detection and possibly treatment of the affected individual and make breeding recommendations to reduce the frequency of the disease in the captive cheetah population; wild cheetahs would also be screened to get a better understanding of the disease in the wild. If no mutation is found as part of this preliminary study, other approaches will be followed.
Scientific exchange, and overview of the team:
- June 2014: CCF delegates Drs Laurie Marker (Founder, Exec Director) and Anne Schmidt-Küntzel (Geneticist, Asst Dir Animal Health & Research) visit NZG to lay down the plan of the collaboration and discuss initial progress.
- June/July 2014: CCF student Ms Lucia Mhuulu visits NZG.
- July 2014: NZG post-doctoral fellow Dr Helene Brettschneider and student Ms Sedzani Manyuha visit CCF.
- Nov 2014: CCF post-doctoral fellow Dr Ezequiel Fabiano visits NZG and participates in NZG symposium.
- May 2015: CCF trainee Ms Gabriella Mulikita visits NZG.
- June 2015: NZG delegates Prof Antoinette Kotze (Manager, Research and Scientific Services), Drs Desire Dalton and Monica Mwale (Geneticists), Emily Lane (Pathologist), and student Mr Antonie Kloppers visit CCF. In addition Prof Karen Terio (Pathologist) from the University of Illinois is invited to the meeting. The current status of the project, next steps, and future collaborations are discussed.