RGD Reference Report - Camk2n1 Is a Negative Regulator of Blood Pressure, Left Ventricular Mass, Insulin Sensitivity, and Promotes Adiposity. - Rat Genome Database

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Camk2n1 Is a Negative Regulator of Blood Pressure, Left Ventricular Mass, Insulin Sensitivity, and Promotes Adiposity.

Authors: Alfazema, Neza  Barrier, Marjorie  de Procé, Sophie Marion  Menzies, Robert I  Carter, Roderick  Stewart, Kevin  Diaz, Ana Garcia  Moyon, Ben  Webster, Zoe  Bellamy, Christopher O C  Arends, Mark J  Stimson, Roland H  Morton, Nicholas M  Aitman, Timothy J  Coan, Philip M 
Citation: Alfazema N, etal., Hypertension. 2019 Sep;74(3):687-696. doi: 10.1161/HYPERTENSIONAHA.118.12409. Epub 2019 Jul 22.
RGD ID: 18899561
Pubmed: PMID:31327268   (View Abstract at PubMed)
PMCID: PMC6686962   (View Article at PubMed Central)
DOI: DOI:10.1161/HYPERTENSIONAHA.118.12409   (Journal Full-text)

Metabolic syndrome is a cause of coronary artery disease and type 2 diabetes mellitus. Camk2n1 resides in genomic loci for blood pressure, left ventricle mass, and type 2 diabetes mellitus, and in the spontaneously hypertensive rat model of metabolic syndrome, Camk2n1 expression is cis-regulated in left ventricle and fat and positively correlates with adiposity. Therefore, we knocked out Camk2n1 in spontaneously hypertensive rat to investigate its role in metabolic syndrome. Compared with spontaneously hypertensive rat, Camk2n1-/- rats had reduced cardiorenal CaMKII (Ca2+/calmodulin-dependent kinase II) activity, lower blood pressure, enhanced nitric oxide bioavailability, and reduced left ventricle mass associated with altered hypertrophic networks. Camk2n1 deficiency reduced insulin resistance, visceral fat, and adipogenic capacity through the altered cell cycle and complement pathways, independent of CaMKII. In human visceral fat, CAMK2N1 expression correlated with adiposity and genomic variants that increase CAMK2N1 expression associated with increased risk of coronary artery disease and type 2 diabetes mellitus. Camk2n1 regulates multiple networks that control metabolic syndrome traits and merits further investigation as a therapeutic target in humans.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Camk2n1Ratdecreased brown adipose tissue mass  IMP  RGD 
Camk2n1em1TjaRatdecreased brown adipose tissue mass  IMP  RGD 
SHR-Camk2n1em1Tja-/-Ratdecreased brown adipose tissue mass  IMP compared to SHR/NCrlRGD 
Camk2n1Ratdecreased epididymal fat pad weight  IMP  RGD 
Camk2n1em1TjaRatdecreased epididymal fat pad weight  IMP  RGD 
SHR-Camk2n1em1Tja-/-Ratdecreased epididymal fat pad weight  IMP compared to SHR/NCrlRGD 
Camk2n1Ratdecreased heart left ventricle weight  IMP  RGD 
Camk2n1em1TjaRatdecreased heart left ventricle weight  IMP  RGD 
SHR-Camk2n1em1Tja-/-Ratdecreased heart left ventricle weight  IMP compared to SHR/NCrlRGD 
Camk2n1Ratdecreased mesenteric fat pad weight  IMP  RGD 
Camk2n1em1TjaRatdecreased mesenteric fat pad weight  IMP  RGD 
SHR-Camk2n1em1Tja-/-Ratdecreased mesenteric fat pad weight  IMP compared to SHR/NCrlRGD 
Camk2n1Ratdecreased retroperitoneal fat pad weight  IMP  RGD 
Camk2n1em1TjaRatdecreased retroperitoneal fat pad weight  IMP  RGD 
SHR-Camk2n1em1Tja-/-Ratdecreased retroperitoneal fat pad weight  IMP compared to SHR/NCrlRGD 
Camk2n1Ratdecreased systemic arterial diastolic blood pressure  IMP  RGD 
Camk2n1em1TjaRatdecreased systemic arterial diastolic blood pressure  IMP  RGD 
SHR-Camk2n1em1Tja-/-Ratdecreased systemic arterial diastolic blood pressure  IMP compared to SHR/NCrlRGD 
Camk2n1Ratdecreased systemic arterial systolic blood pressure  IMP  RGD 
Camk2n1em1TjaRatdecreased systemic arterial systolic blood pressure  IMP  RGD 
SHR-Camk2n1em1Tja-/-Ratdecreased systemic arterial systolic blood pressure  IMP compared to SHR/NCrlRGD 
Objects Annotated

Genes (Rattus norvegicus)
Camk2n1  (calcium/calmodulin-dependent protein kinase II inhibitor 1)
Camk2n1em1Tja  (calcium/calmodulin-dependent protein kinase II inhibitor 1; ZFN induced mutant 1, Tja)

Strains
SHR-Camk2n1em1Tja-/-  (SHR-Camk2n1em1Tja-/Camk2n1em1Tja-)

Objects referenced in this article
Strain SHR/NCrl null Rattus norvegicus

Additional Information