RGD Reference Report - Heterozygous connexin 50 mutation affects metabolic syndrome attributes in spontaneously hypertensive rat. - Rat Genome Database

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Heterozygous connexin 50 mutation affects metabolic syndrome attributes in spontaneously hypertensive rat.

Authors: Šeda, Ondřej  Křenová, Drahomíra  Oliyarnyk, Olena  Šedová, Lucie  Krupková, Michaela  Liška, František  Chylíková, Blanka  Kazdová, Ludmila  Křen, Vladimír 
Citation: Šeda O, etal., Lipids Health Dis. 2016 Nov 21;15(1):199. doi: 10.1186/s12944-016-0376-3.
RGD ID: 150429989
Pubmed: PMID:27871290   (View Abstract at PubMed)
PMCID: PMC5117636   (View Article at PubMed Central)
DOI: DOI:10.1186/s12944-016-0376-3   (Journal Full-text)


BACKGROUND: Several members of connexin family of transmembrane proteins were previously implicated in distinct metabolic conditions. In this study we aimed to determine the effects of complete and heterozygous form of connexin50 gene (Gja8) mutation L7Q on metabolic profile and oxidative stress parameters in spontaneously hypertensive inbred rat strain (SHR).
METHODS: Adult, standard chow-fed male rats of SHR, heterozygous SHR-Dca+/- and SHR-Dca-/- coisogenic strains were used. At the age of 4 months, dexamethasone (2.6 μg/ml) was administered in the drinking water for three days. The lipidemic profile (cholesterol and triacylglycerol concentration in 20 lipoprotein fractions, chylomicron, VLDL, LDL and HDL particle sizes) together with 33 cytokines and hormones in serum and several oxidative stress parameters in plasma, liver, kidney and heart were assessed.
RESULTS: SHR and SHR-Dca-/- rats had similar concentrations of triacylglycerols and cholesterol in all major lipoprotein fractions. The heterozygotes reached significantly highest levels of total (SHR-Dca+/-: 51.3 ± 7.2 vs. SHR: 34.5 ± 2.4 and SHR-Dca-/-: 34.4 ± 2.5 mg/dl, p = 0.026), chylomicron and VLDL triacylglycerols. The heterozygotes showed significantly lowest values of HDL cholesterol (40.9 ± 2.3 mg/dl) compared both to SHR (51.8 ± 2.2 mg/dl) and SHR-Dca-/- (48.6 ± 2.7 mg/dl). Total and LDL cholesterol in SHR-Dca+/- was lower compared to SHR. Glucose tolerance was improved and insulin concentrations were lowest in SHR-Dca-/- (1.11 ± 0.20 pg/ml) in comparison with both SHR (2.32 ± 0.49 pg/ml) and SHR-Dca+/- (3.04 ± 0.21 pg/ml). The heterozygous rats showed profile suggestive of increased oxidative stress as well as highest serum concentrations of several pro-inflammatory cytokines including interleukins 6, 12, 17, 18 and tumor necrosis factor alpha.
CONCLUSIONS: Our results demonstrate that connexin50 mutation in heterozygous state affects significantly the lipid profile and the oxidative stress parameters in the spontaneously hypertensive rat strain.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Gja8Ratregulation of catalase activity  IMP  RGD 
Gja8Ratregulation of glutathione peroxidase activity  IMP  RGD 
Gja8Ratregulation of granulocyte macrophage colony-stimulating factor production  IMP  RGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Gja8Ratdecreased circulating HDL cholesterol level  IAGP  RGD 
Gja8m1CubRatdecreased circulating HDL cholesterol level  IAGP  RGD 
SHR-Gja8m1+/-CubRatdecreased circulating HDL cholesterol level  IAGP  RGD 
Gja8Ratdecreased circulating insulin level  IAGP  RGD 
Gja8m1CubRatdecreased circulating insulin level  IAGP  RGD 
SHR-Gja8m1-/-CubRatdecreased circulating insulin level  IAGP  RGD 
Gja8Ratdecreased circulating LDL cholesterol level  IAGP  RGD 
Gja8m1CubRatdecreased circulating LDL cholesterol level  IAGP  RGD 
SHR-Gja8m1+/-CubRatdecreased circulating LDL cholesterol level  IAGP  RGD 
Gja8Ratdecreased epididymal fat pad weight  IAGP  RGD 
Gja8m1CubRatdecreased epididymal fat pad weight  IAGP  RGD 
SHR-Gja8m1-/-CubRatdecreased epididymal fat pad weight  IAGP  RGD 
Gja8Ratdecreased fasting circulating glucose level inducesIAGPglucose and controlled dexamethasone content drinking water RGD 
Gja8m1CubRatdecreased fasting circulating glucose level inducesIAGPglucose and controlled dexamethasone content drinking water RGD 
SHR-Gja8m1+/-CubRatdecreased fasting circulating glucose level inducesIAGPglucose and controlled dexamethasone content drinking water RGD 
SHR-Gja8m1-/-CubRatdecreased fasting circulating glucose level inducesIAGPglucose and controlled dexamethasone content drinking water RGD 
Gja8Ratdecreased glutathione level  IAGP  RGD 
Gja8m1CubRatdecreased glutathione level  IAGP  RGD 
SHR-Gja8m1+/-CubRatdecreased glutathione level  IAGP  RGD 
SHR-Gja8m1-/-CubRatdecreased glutathione level  IAGP  RGD 
Gja8Ratdecreased glutathione peroxidase activity  IAGP  RGD 
Gja8m1CubRatdecreased glutathione peroxidase activity  IAGP  RGD 
SHR-Gja8m1+/-CubRatdecreased glutathione peroxidase activity  IAGP  RGD 
Gja8Ratdecreased glutathione reductase level  IAGP  RGD 
Gja8m1CubRatdecreased glutathione reductase level  IAGP  RGD 
SHR-Gja8m1+/-CubRatdecreased glutathione reductase level  IAGP  RGD 
Gja8Ratdecreased superoxide dismutase level  IAGP  RGD 
Gja8m1CubRatdecreased superoxide dismutase level  IAGP  RGD 
SHR-Gja8m1+/-CubRatdecreased superoxide dismutase level  IAGP  RGD 
SHR-Gja8m1-/-CubRatdecreased superoxide dismutase level  IAGP  RGD 
Gja8Rathyperchylomicronemia  IAGP  RGD 
Gja8m1CubRathyperchylomicronemia  IAGP  RGD 
SHR-Gja8m1+/-CubRathyperchylomicronemia  IAGP  RGD 
Gja8Ratincreased catalase level  IAGP  RGD 
Gja8m1CubRatincreased catalase level  IAGP  RGD 
SHR-Gja8m1+/-CubRatincreased catalase level  IAGP  RGD 
Gja8Ratincreased circulating CCL3 level  IAGP  RGD 
Gja8m1CubRatincreased circulating CCL3 level  IAGP  RGD 
SHR-Gja8m1+/-CubRatincreased circulating CCL3 level  IAGP  RGD 
Gja8Ratincreased circulating insulin level  IAGP  RGD 
Gja8m1CubRatincreased circulating insulin level  IAGP  RGD 
SHR-Gja8m1+/-CubRatincreased circulating insulin level  IAGP  RGD 
Gja8Ratincreased circulating interleukin-17 level  IAGP  RGD 
Gja8m1CubRatincreased circulating interleukin-17 level  IAGP  RGD 
SHR-Gja8m1+/-CubRatincreased circulating interleukin-17 level  IAGP  RGD 
Gja8Ratincreased circulating triglyceride level  IAGP  RGD 
Gja8m1CubRatincreased circulating triglyceride level  IAGP  RGD 
SHR-Gja8m1+/-CubRatincreased circulating triglyceride level  IAGP  RGD 
Gja8Ratincreased circulating tumor necrosis factor level  IAGP  RGD 
Gja8m1CubRatincreased circulating tumor necrosis factor level  IAGP  RGD 
SHR-Gja8m1+/-CubRatincreased circulating tumor necrosis factor level  IAGP  RGD 
Gja8Ratincreased epididymal fat pad weight  IAGP  RGD 
Gja8m1CubRatincreased epididymal fat pad weight  IAGP  RGD 
SHR-Gja8m1+/-CubRatincreased epididymal fat pad weight  IAGP  RGD 
Gja8Ratincreased interleukin-12 secretion  IAGP  RGD 
Gja8m1CubRatincreased interleukin-12 secretion  IAGP  RGD 
SHR-Gja8m1+/-CubRatincreased interleukin-12 secretion  IAGP  RGD 
Gja8Ratincreased interleukin-18 secretion  IAGP  RGD 
Gja8m1CubRatincreased interleukin-18 secretion  IAGP  RGD 
SHR-Gja8m1+/-CubRatincreased interleukin-18 secretion  IAGP  RGD 
Gja8Ratincreased interleukin-6 secretion  IAGP  RGD 
Gja8m1CubRatincreased interleukin-6 secretion  IAGP  RGD 
SHR-Gja8m1+/-CubRatincreased interleukin-6 secretion  IAGP  RGD 
Objects Annotated

Genes (Rattus norvegicus)
Gja8  (gap junction protein, alpha 8)
Gja8m1Cub  (gap junction protein, alpha 8; mutant 1 Cub)


Additional Information