Humans of early West African ancestry are more prone to kidney dysfunction. Earlier studies demonstrate that the reason for this phenomenon is because of the mutation of APOL 1 gene in most humans of early West African ancestry. Although several APOL genes are expressed in mammals, APOL 1 is only naturally expressed in primates. The restricted expression of APOL 1 to only primates has limited the exploration of the functional role of APOL1 variants in kidney disease development. The aim of this preliminary study was to develop a guinea pig model of APOL1 variants and demonstrate possible biological basis of APOL 1-mediated kidney injury as is observed in humans given that both humans and guinea pigs are HDL mammals.
Expression of APOL1 gene variants in Guinea pigs was done by hydrodynamic gene delivery (HGD). 5 sets of male and female guinea pigs were injected with plasmids containing various APOL1 gene variants. APOL1 protein presence in Guinea pig plasma and kidney tissues was determined by WESTERN blotting and immunohistochemistry (IHC) respectively.
Induction with APOL1 gene variant in Guinea pigs resulted in a derangement of renal function as evidenced by creatinine accumulation and distorted renal histoarchitecture. There was a scattered inconsistent IHC staining for APOL1 in the experimental group although the WESTERN blot assay showed a consistently elevated protein presence in the same group compared to control. Subsequent studies will seek to improve on the APOL1 induction method, gather more genetic information in addition to determining the full extent of renal structure and function compromise in the Guinea pig specie.