RGD Reference Report - Targeted disruption of Adamts16 gene in a rat genetic model of hypertension. - Rat Genome Database

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Targeted disruption of Adamts16 gene in a rat genetic model of hypertension.

Authors: Gopalakrishnan, K  Kumarasamy, S  Abdul-Majeed, S  Kalinoski, AL  Morgan, EE  Gohara, AF  Nauli, SM  Filipiak, WE  Saunders, TL  Joe, B 
Citation: Gopalakrishnan K, etal., Proc Natl Acad Sci U S A. 2012 Dec 11;109(50):20555-9. doi: 10.1073/pnas.1211290109. Epub 2012 Nov 26.
RGD ID: 9685162
Pubmed: PMID:23185005   (View Abstract at PubMed)
PMCID: PMC3528556   (View Article at PubMed Central)
DOI: DOI:10.1073/pnas.1211290109   (Journal Full-text)

A disintegrin-like metalloproteinase with thrombospondin motifs-16 (Adamts16) is an important candidate gene for hypertension. The goal of the present study was to further assess the candidacy of Adamts16 by targeted disruption of this gene in a rat genetic model of hypertension. A rat model was generated by manipulating the genome of the Dahl Salt-sensitive (S) rat using zinc-finger nucleases, wherein the mutant rat had a 17 bp deletion in the first exon of Adamts16, introducing a stop codon in the transcript. Systolic blood pressure (BP) of the homozygous Adamts16(mutant) rats was lower by 36 mmHg compared with the BP of the S rats. The Adamts16(mutant) rats exhibited significantly lower aortic pulse wave velocity and vascular media thickness compared with S rats. Scanning electron and fluorescence microscopic studies indicated that the mechanosensory cilia of vascular endothelial cells from the Adamts16(mutant) rats were longer than that of the S rats. Furthermore, Adamts16(mutant) rats showed splitting and thickening of glomerular capillaries and had a longer survival rate, compared with the S rats. Taken together, these physiological observations functionally link Adamts16 to BP regulation and suggest the vasculature as the potential site of action of Adamts16 to lower BP.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
hypertension  ISOAdamts16 (Rattus norvegicus)9685162; 9685162 RGD 
hypertension  IMP 9685162; 9685162; 9685162 RGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
regulation of cilium assembly  IMP 9685162 RGD 
regulation of systemic arterial blood pressure  IMP 9685162 RGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
decreased systemic arterial diastolic blood pressure  IMP 9685162; 9685162; 9685162As compared to SS parentsRGD 
decreased systemic arterial systolic blood pressure  IMP 9685162; 9685162; 9685162As compared to SS parentsRGD 
extended life span  IMP 9685162; 9685162; 9685162As compared to SS parentsRGD 
increased urine protein level  IMP 9685162; 9685162; 9685162As compared to SS parentsRGD 
thin ventricular wall  IMP 9685162; 9685162; 9685162As compared to SS parentsRGD 
Objects Annotated

Genes (Rattus norvegicus)
Adamts16  (ADAM metallopeptidase with thrombospondin type 1 motif, 16)
Adamts16em1Bj  (ADAM metallopeptidase with thrombospondin type 1 motif, 16; ZFN mutant1,Bj)

Genes (Mus musculus)
Adamts16  (ADAM metallopeptidase with thrombospondin type 1 motif 16)

Genes (Homo sapiens)
ADAMTS16  (ADAM metallopeptidase with thrombospondin type 1 motif 16)

Strains
SS-Adamts16em1Bj  (NA)


Additional Information