Developmental expression of human angiotensinogen in transgenic
mice.
Yang, Gongyu, and Curt D. Sigmund.
Department of Anatomy & Cell Biology, Departments of Internal
Medicine and Physiology & Biophysics, The University of Iowa College
of Medicine, Iowa City, Iowa 52242
APStracts 5:0032F, 1998.
Transgenic mice containing the human angiotensinogen (HAGT) gene were
utilized to determine the developmental regulation of HAGT
expression. RNase protection assay on total RNA obtained from whole
transgenic fetuses revealed that HAGT expression was first detected
at embryonic day 8.5 (E8.5) and was abundant from E9.5 onward. The
earliest expression of the HAGT transgene appeared to precede the
earliest expression of the endogenous mouse AGT gene by 1-2 days.
Northern blot analysis revealed moderate levels of HAGT mRNA in liver
and kidney, and low levels of HAGT mRNA in heart and brain from E16.5
days of gestation onward. HAGT mRNA in liver, while abundant during
late gestation and in 2-week old and adult mice, decreased
transiently around birth. In situ hybridization performed on sections
from whole fetuses revealed that HAGT mRNA was restricted to the
developing liver and heart between E9.5-E11.5 but became more
widespread to include the developing aorta, brain, subcutaneous
tissues, and vertebra at E13.5. In situ hybridization analysis on
fetal kidneys from late gestation, newborn and two-week old mice
demonstrated a progressive restriction of HAGT mRNA to developing
cortical proximal tubular cells. These data illustrate the
developmental tissue-specific regulation of HAGT expression and
demonstrate that sequences present in the transgene can confer an
appropriate developmental expression profile.
Received 12 November 1997; accepted in final form 2 February
1998.
APS Manuscript Number F355-7.
Article publication pending Am. J. Physiol. (Renal Physiology).
ISSN 1080-4757 Copyright 1998 The American Physiological Society.
Published in APStracts on 19 February 1998