RGD Reference Report - Atherogenesis and metabolic dysregulation in LDL receptor-knockout rats. - Rat Genome Database

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Atherogenesis and metabolic dysregulation in LDL receptor-knockout rats.

Authors: Sithu, Srinivas D  Malovichko, Marina V  Riggs, Krista A  Wickramasinghe, Nalinie S  Winner, Millicent G  Agarwal, Abhinav  Hamed-Berair, Rihab E  Kalani, Anuradha  Riggs, Daniel W  Bhatnagar, Aruni  Srivastava, Sanjay 
Citation: Sithu SD, etal., JCI Insight. 2017 May 4;2(9). pii: 86442. doi: 10.1172/jci.insight.86442.
RGD ID: 12910100
Pubmed: PMID:28469073   (View Abstract at PubMed)
PMCID: PMC5414561   (View Article at PubMed Central)
DOI: DOI:10.1172/jci.insight.86442   (Journal Full-text)

Mechanisms of atherogenesis have been studied extensively in genetically engineered mice with disturbed cholesterol metabolism such as those lacking either the LDL receptor (Ldlr) or apolipoprotein E (apoe). Few other animal models of atherosclerosis are available. WT rabbits or rats, even on high-fat or high-cholesterol diets, develop sparse atherosclerotic lesions. We examined the effects of Ldlr deletion on lipoprotein metabolism and atherosclerotic lesion formation in Sprague-Dawley rats. Deletion of Ldlr resulted in the loss of the LDLR protein and caused a significant increase in plasma total cholesterol and triglycerides. On normal chow, Ldlr-KO rats gained more weight and were more glucose intolerant than WT rats. Plasma proprotein convertase subtilisin kexin 9 (PCSK9) and leptin levels were higher and adiponectin levels were lower in KO than WT rats. On the Western diet, the KO rats displayed exaggerated obesity and age-dependent increases in glucose intolerance. No appreciable aortic lesions were observed in KO rats fed normal chow for 64 weeks or Western diet for 16 weeks; however, after 34-52 weeks of Western diet, the KO rats developed exuberant atherosclerotic lesions in the aortic arch and throughout the abdominal aorta. The Ldlr-KO rat may be a useful model for studying obesity, insulin resistance, and early-stage atherosclerosis.

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Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
positive regulation of triglyceride catabolic process  IMP 12910100 RGD 

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Measurement Methods:
Objects Annotated

Genes (Rattus norvegicus)
Ldlr  (low density lipoprotein receptor)
Ldlrem1Sage  (low density lipoprotein receptor; ZFN induced mutant 1, Sage)

Genes (Mus musculus)
Ldlr  (low density lipoprotein receptor)

Genes (Homo sapiens)
LDLR  (low density lipoprotein receptor)

SD-Ldlrem1Sage  (NA)

Additional Information