Role of beta-dystrobrevin in nonmuscle dystrophin-associated protein complex-like complexes in kidney and liver

beta -Dystrobrevin is a dystrophin-related and -associated protein that is highly expressed in brain, kidney, and liver. Recent studies with the kidne ys of the mdx3Cv mouse, which lacks all dystrophin isoforms, suggest that b eta -dystrobrevin, and not the dystrophin isoforms, may be the key componen t in the assembly of complexes similar to the muscle dystrophin-associated protein complexes (DPC) in nonmuscle tissues. To understand the role of bet a -dystrobrevin in the function of nonmuscle tissues, we generated beta -dy strobrevin-deficient (dtnb(-/-)) mice by gene targeting. dtnb(-/-) mice are healthy, fertile, and normal in appearance. No beta -dystrobrevin was dete cted in these mice by Western blotting or immunocytochemistry. In addition, the levels of several beta -dystrobrevin-interacting proteins, namely Dp71 isoforms and the syntrophins, were greatly reduced from the basal membrane s of kidney tubules and liver sinusoids and on Western blots of crude kidne y and liver microsomes of beta -dystrobrevin-deficient mice. However, no ab normality was detected in the ultrastructure of membranes of kidney and liv er cells or in the renal function of these mice. beta -Dystrobrevin may the refore be an anchor or scaffold for Dp71 and syntrophin isoforms, as well a s other associating proteins at the basal membranes of kidney and liver, bu t is not necessary for the normal function of these mice.