Targeting deletion of angiotensin type 1B receptor gene in the mouse.
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- to 8-wk-old Agtr1b -/- mice, high AT1B transcriptional activity was observed in adrenal zona glomerulosa cells and the testis, including mature and immature spermatic cells, whereas 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.
Chen
X
X
Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
Li
W
W
Yoshida
H
H
Tsuchida
S
S
Nishimura
H
H
Takemoto
F
F
Okubo
S
S
Fogo
A
A
Matsusaka
T
T
Ichikawa
I
I
D000450:Aldosterone / Q000097:blood; D000818:Animals; D001794:Blood Pressure; D002831:Choroid Plexus / Q000378:metabolism; D005091:Exons; D017930:Genes, Reporter; D006580:Genetic Carrier Screening; D005822:Genetic Vectors; D005838:Genotype; D006720:Homozygote; D007763:Lac Operon; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010903:Pituitary Gland, Anterior / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics; D012982:Sodium, Dietary; D013094:Spermatozoa / Q000378:metabolism; D013737:Testis / Q000378:metabolism; D014158:Transcription, Genetic; D015384:Zona Glomerulosa / Q000378:metabolism; D001616:beta-Galactosidase / Q000096:biosynthesis
D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin; D012982:Sodium, Dietary; D000450:Aldosterone; D001616:beta-Galactosidase