Bone marrow transplantation rescues Alport mice*

Keywords: Alport’s syndrome; basement membrane;bone marrow transplantationIn the 9 May 2006 issue of Proc Natl Acad Sci USA,Sugimoto and colleagues [1] described fascinating dataon a potential approach to treat Alport’s syndrome, arare genetic disease leading to renal failure, which so farcould not be cured. The work was highly publicized anddiscussed in both scientific journals and the lay press.Alport’s syndrome derives from a mutation of eitherthe a3, a4ora5 chain of type IV collagen, i.e. collagentypes that constitute basement membranes in the renalglomerulus, the ear and the eye. Mice that aregenetically deficient of the a3(IV)-chain (‘Alportmice’) develop a renal phenotype very similar to thatof Alport patients (Figure 1), i.e. proteinuria, glomer-ulonephritis and subsequent tubulointerstitial fibrosisstarting at 8 weeks of age and leading to death due torenal failure at 20–23 weeks. In the study by Sugimotoet al. [1], 8 week-old Alport mice were lethallyirradiated and then received an allogenic unfraction-ated bone marrow transplant from either LacZ mice,i.e. mice with a normal collagen production plusexpression of the LacZ marker in all cells, or fromanother Alport mouse. Whereas the latter had no effecton the phenotype, the allogenic bone marrow led tomarkedly reduced proteinuria upon follow-up, andimproved renal function as well as renal histology.LacZ-positive cells constituted about 10% of theglomerular cells and were found in podocyte andmesangial cell locations. The glomerular stainingpattern for the a3- and a5(IV) chains was partiallyrestored. If these data can be confirmed and extendedby showing that the treatment delays death from renalfailure in Alport mice (see subsequently), there wouldbe several major implications of this study.