Abstract
The B family of Eph receptor tyrosine kinases and their ephrin ligands, best known for their role in the development of the nervous and vascular systems, have recently been implicated in mammalian kidney development and maintenance. However, the renal expression and function of the EphA and ephrin-A families have not been investigated. We performed immunohistochemistry for ephrin-A2 and ephrin-A5 in kidneys of normal adult wildtype (WT) mice and carried out quantitative morphological analysis of renal corpuscles and tubules in haematoxylin- and eosin-stained sections of WT, ephrin-A2-/-, ephrin-A5-/-and ephrin-A2A5-/-(knockout) mice. Ephrin-A2 and ephrin-A5 were strongly expressed in the tubules and glomeruli of the adult mouse kidney. Despite the significant overlap in expression between the two proteins, only the lack of ephrin-A5 had an effect on kidney morphology with glomerular size being mildly reduced in mice lacking the gene for ephrin-A5. However, the magnitude of this change was very small and could only be detected when animals were pooled across genotypes lacking ephrin-A5. The subtle phenotype, together with the relatively infrequent incidence of kidney failure in our breeding colony, suggest that ephrin-A2 and ephrin-A5 play only minor roles in kidney development and function. It is likely that other members of the ephrin-A family are expressed in the mouse kidney and redundancy within this large family of “promiscuous” signalling molecules may compensate for the loss of individual proteins in knockout mice.
Highlights
Normal kidney development and function requires coordinated cell signalling through complex molecular pathways[1]
Immunohistochemistry for ephrin-A2 and ephrin-A5 Ephrin-A2 and ephrin-A5 expression patterns were examined in the adult mouse kidney using immunohistochemistry (Figure 1)
In summary, we show strong expression of ephrin-A2 and ephrin-A5 in the tubules and glomeruli of the adult mouse kidney
Summary
Normal kidney development and function requires coordinated cell signalling through complex molecular pathways[1]. The Eph receptor tyrosine kinases and their ephrin ligands, best known for their role in the development of the nervous and vascular systems, have recently been implicated in mammalian kidney development and maintenance[2,3,4]. EphBs and ephrin-Bs have been implicated in the development and maintenance of the slit diaphragm[2], a component of the filtration barrier in the glomerulus, and in renal tubule development[4]. The expression and function of the other family of ligands, the ephrin-As, has not been investigated
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