Targeting deletion of angiotensin type 1b receptor gene in the
mouse .
Chen, Hiangmei, Wenge Li, Hiroaki Yoshida, Shinya Tsuchida, Hideki
Nishimura, Fumi Takemoto, Soichiro Okubo, Agnes Fogo, Taiji
Matsusaka, and Iekuni Ichikawa.
Departments of Pediatrics and Pathology, Vanderbilt University
School of Medicine, Nashville, TN 37232
APStracts 3:0218F, 1996.
We null-mutated the mouse angiotensin type 1B (AT1B) receptor gene
(Agtr1b) by gene targeting. To identify the specific cell types
carrying high Agtr1b gene transcriptional activities, the AT1B coding
exon was replaced with a reporter gene, lacZ. In 6-8 week old Agtr1b
-/- mice, high AT1B transcriptional activity was observed in adrenal
zona glomerulosa cells, the testis, including mature and immature
spermatic cells; while low activity was detected homogeneously in
anterior pituitary cells and choroidal plexus vessel walls. A similar
pattern was observed in Agtr1b +/- mice with less intensity.
Microscopically, the anterior pituitary, heart, adrenal, zona
glomerulosa, kidney and the testis of Agtr1b -/- mice were intact,
and were indistinguishable from those of Agtr1b +/+ mice. Systemic
blood pressure was comparable in Agtr1b -/- and Agtr1b +/+ mice.
Moreover, plasma aldosterone level was comparable between the two
mouse groups. No compensatory enhancement of AT1A mRNA was found in
the kidney and adrenal gland of Agtr1b -/- mice. The observed absence
of the abnormal phenotypes in Agtr1b -/- mice which have been
described for homozygous angiotensinogen null mutant mice indicates
that 1) AT1A receptors can take over the role of AT1B receptors in
Agtr1b -/- mice, or 2) functionally significant non-AT1, non-AT2
receptor(s) may exist for the action of angiotensin.
Received 23 July 1996; accepted in final form 13 November 1996.
APS Manuscript Number F211-6.
Article publication pending Am. J. Physiol. (Renal Fluid Electrolyte
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 31 December 1996