RGD Reference Report - Murine double nullizygotes of the angiotensin type 1A and 1B receptor genes duplicate severe abnormal phenotypes of angiotensinogen nullizygotes. - Rat Genome Database

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Murine double nullizygotes of the angiotensin type 1A and 1B receptor genes duplicate severe abnormal phenotypes of angiotensinogen nullizygotes.

Authors: Tsuchida, S  Matsusaka, T  Chen, X  Okubo, S  Niimura, F  Nishimura, H  Fogo, A  Utsunomiya, H  Inagami, T  Ichikawa, I 
Citation: Tsuchida S, etal., J Clin Invest 1998 Feb 15;101(4):755-60.
RGD ID: 737778
Pubmed: PMID:9466969   (View Abstract at PubMed)
PMCID: PMC508622   (View Article at PubMed Central)
DOI: DOI:10.1172/JCI1899   (Journal Full-text)

Rodents are the unique species carrying duplicated angiotensin (Ang) type 1 (AT1) receptor genes, Agtr1a and Agtr1b. After separately generating Agtr1a and Agtr1b null mutant mice by gene targeting, we produced double mutant mice homozygous for both Agtr1a and Agtr1b null mutation (Agtr1a-/-; Agtr1b-/-) by mating the single gene mutants. Agtr1a-/-, Agtr1b-/- mice are characterized by normal in utero survival but decreased ex utero survival rate. After birth they are characterized by low body weight gain, marked hypotension, and abnormal kidney morphology including delayed maturity in glomerular growth, hypoplastic papilla, and renal arterial hypertrophy. These abnormal phenotypes are quantitatively similar to those found in mutant mice homozygous for the angiotensinogen gene (Agt-/-), indicating that major biological functions of endogenous Ang elucidated by the abnormal phenotypes of Agt-/- are mediated by the AT1 receptors. Infusion of Ang II, AT1 blockers, or an AT2 blocker was without effect on blood pressure in Agtr1a-/-; Agtr1b-/- mice, indicating that AT2 receptor does not exert acute depressor effects in these mice lacking AT1 receptors. Also, unlike Agt-/- mice, some Agtr1a-/-; Agtr1b-/- mice have a large ventricular septum defect, suggesting that another receptor such as AT2 is functionally activated in Agtr1a-/-, Agtr1b-/- mice.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Hypotension  ISOAgt (Mus musculus)737778; 737778 RGD 
Hypotension  IMP 737778 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Agt  (angiotensinogen)

Genes (Mus musculus)
Agt  (angiotensinogen)

Genes (Homo sapiens)
AGT  (angiotensinogen)

Objects referenced in this article
Gene AGTR1 angiotensin II receptor type 1 Homo sapiens
Gene AP2S1 adaptor related protein complex 2 subunit sigma 1 Homo sapiens
Gene Agtr1a angiotensin II receptor, type 1a Mus musculus
Gene Agtr1b angiotensin II receptor, type 1b Mus musculus
Gene Ap2s1 adaptor related protein complex 2 subunit sigma 1 Rattus norvegicus

Additional Information