Humanized Mouse Model for Minimal Change Disease

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Identifying the “permeability factor” for patients with FSGS or minimal change disease has been one of the “holy grails” of nephrology, and our inability to identify such a factor has not been for any lack of trying.  One of the obstacles in studying this disease is the lack of good animal models to study it.

A French group published a 2007 JASN article describing a mouse model of immune-mediated nephrotic syndrome which perhaps gives us some mechanistic insight into the cause of the disease.  In this paper, researchers took CD34+ T-cells from humans with steroid-resistant nephrotic syndrome.  They then injected these T-cells either (a) intraperitoneally, or (b) intraosseously–that is, directly into the bone marrow.  In the case of intraperitoneal injections, the existence of circulating “humanized” T-cells could be demonstrated, but they eventually went away over time as the engraftment was not permanent.  These mice did not get proteinuria.  In the case of intraosseous injections, these T-cells could be demonstrated to engraft permanently, albeit at a low frequency.  Interestingly, these mice developed significant albuminuria and foot process effacement, suggesting that this could be used as a mouse model of disease.  
What is particularly interesting about this experiment is the idea that the “permeability factor” is transferable only with T-cell precursors–and not with peripheral T-cells.  So perhaps the permeability factor comes from the bone marrow, rather than activated T-cell responses…

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