**9. Conclusions**

Given the wide heterogeneity of IgAN clinical features added to the multifactorial aspect of the pathology, the development of experimental models constitutes a huge challenge for researchers. Since 1979, several animal models have been developed for a better understanding of IgAN pathogenesis. Although multiple models were able to reproduce some of the IgAN characteristics, they could not cover the full spectrum of pathological manifestations observed in patients. It is evident that animal models can constitute useful tools, taking into consideration marked differences between human and mouse systems especially in IgA biosynthesis, dominant circulating forms, molecules halflife and clearance mechanisms [18]. Most importantly, murine IgA resembles human IgA2 lacking the hinge region and O-glycans which limit the utility of glycosylation aberrancy studies in mouse models. Despite these structural and immunological differences between

humans and mice, experimental models developed so far have elucidated some enigmas about IgAN onset and progression.

The heterogeneity of human disease and animal models likely reflects the varying influence of genetic and environmental factors on a multitude of complex pathogenic mechanisms modulating the disease phenotype in different individuals and populations. Another explanation is that IgAN may not be a "single disease" but rather a group of distinct diseases showing a common path of mesangial IgA deposition.

**Author Contributions:** Conceptualization, B.W. and J.-C.A.; writing—original draft preparation, B.W.; writing—review and editing J.-C.A., M.C., L.Z. and V.P.; supervision and consultation, J.-C.A. and M.C. All authors have read and agreed to the published version of the manuscript.

**Funding:** This review was funded by grants from <sup>R</sup>égion Nouvelle-Aquitaine (appel d'offre 2017); Chaire d'Immuno-pathologie des Maladies Rénales, Limoges University and Association Limousine pour l'Utilisation du Rein Artificiel à Domicile.

**Conflicts of Interest:** The authors declare no conflict of interest.
