Focal and segmental glomerulosclerosis in mice with podocyte-specific expression of mutant alpha-actinin-4.

Mutations in the gene encoding alpha-actinin-4 (ACTN4), an actin crosslinking protein, are associated with a form of autosomal dominant focal segmental glomerulosclerosis (FSGS). To better study its progression, a transgenic mouse model was developed by expressing murine alpha-actinin-4 containing a mutation analogous to that affecting a human FSGS family in a podocyte-specific manner using the murine nephrin promoter. Consistent with human ACTN4-associated FSGS, which shows incomplete penetrance, a proportion of the transgenic mice exhibited significant albuminuria (8 of 18), while the overall average systolic BP was elevated in both proteinuric and non-proteinuric ACTN4-mutant mice.

PGE2 reduces arachidonic acid release in murine podocytes: evidence for an autocrine feedback loop.

Increased glomerular prostaglandin E(2) (PGE(2)) production is associated with the progression of diseases such as membranous nephropathy, nephrotic syndrome, and anti-Thy1 nephritis. We investigated the signaling pathways that regulate the synthesis and actions of PGE(2) in glomerular podocytes. To study its actions, we assessed the ability of PGE(2) to regulate the production of its own precursor, arachidonic acid (AA), in a mouse podocyte cell line.