The darpp-32 promoter directs transgene expression to the renal
thick ascending limb of the loop of henle.
Blau, Susana, Leanne Daly, Allen Fienberg, Gladys Teitelman, and
Michelle E. Ehrlich.
Departments of Psychiatry and Cell Biology, New York University
Medical Center, New York, New York 10016, The Nathan Kline Institute,
Orangeburg, New York 10962, Laboratory of Molecular and Cellular
Neuroscience, The Rockefeller University, New York, New York 10021,
Department of Anatomy and Cell Biology, SUNY Health Science Center at
Brooklyn, Brooklyn, New York 11203
APStracts 2:0076F, 1995.
DARPP-32, a dopamine- and cyclic AMP-regulated inhibitor of protein
phosphatase-1, is highly co-localized with neuronal and non-neuronal
D1-type receptors. DARPP-32 concentration is enriched in the renal
outer medulla and in the medium size spiny neurons of the brain. In
the ascending limb of the loop of Henle, DARPP-32 is phosphorylated
following stimulation by dopamine and other first messengers, and in
this form, inhibits the activity of the Na+-K+-ATPase pump. For
functional analysis of the DARPP-32 promoter in the kidney, we
characterized the murine gene. There are two groups of transcription
start sites utilized in the brain, but the proximal set appears to be
preferentially used in the kidney. In 4/4 lines of mice carrying a
DARPP-32/lacZ transgene with 2.1Kb of 5'-flanking DNA, adult kidney
lacZ transgene expression mimicked that of endogenous DARPP-32. There
was no ectopic expression in peripheral organs. We conclude that the
sequences necessary for direction of DARPP-32 expression to the mTAL
are contained within this 2.1 Kb fragment
Received 8 January 1995; accepted in final form 2 May 1995.
APS Manuscript Number F2-5.
Article publication pending Am. J. Physiol. (Renal Fluid Electrolyte
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 9 May 1995.