RGD Reference Report - The missense mutation in Abcg5 gene in spontaneously hypertensive rats (SHR) segregates with phytosterolemia but not hypertension. - Rat Genome Database

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The missense mutation in Abcg5 gene in spontaneously hypertensive rats (SHR) segregates with phytosterolemia but not hypertension.

Authors: Chen, J  Batta, A  Zheng, S  Fitzgibbon, WR  Ullian, ME  Yu, H  Tso, P  Salen, G  Patel, SB 
Citation: Chen J, etal., BMC Genet. 2005 Jul 18;6:40.
RGD ID: 1598659
Pubmed: PMID:16026620   (View Abstract at PubMed)
PMCID: PMC1190168   (View Article at PubMed Central)
DOI: DOI:10.1186/1471-2156-6-40   (Journal Full-text)

BACKGROUND: Sitosterolemia is a recessively inherited disorder in humans that is associated with premature atherosclerotic disease. Mutations in ABCG5 or ABCG8, comprising the sitosterolemia locus, STSL, are now known to cause this disease. Three in-bred strains of rats, WKY, SHR and SHRSP, are known to be sitosterolemic, hypertensive and they carry a missense 'mutation' in a conserved residue of Abcg5, Gly583Cys. Since these rat strains are also know to carry mutations at other genetic loci and the extent of phytosterolemia is only moderate, it is important to verify that the mutations in Abcg5 are causative for phytosterolemia and whether they contribute to hypertension. METHODS: To investigate whether the missense change in Abcg5 is responsible for the sitosterolemia we performed a segregation analysis in 103 F2 rats from a SHR x SD cross. Additionally, we measured tail-cuff blood pressure and measured intestinal lipid transport to identify possible mechanisms whereby this mutation causes sitosterolemia. RESULTS: Segregation analysis showed that the inheritance of the Gly583Cys mutation Abcg5 segregated with elevated plant sterols and this pattern was recessive, proving that this genetic change is responsible for the sitosterolemia in these rat strains. Tail-cuff monitoring of blood pressure in conscious animals showed no significant differences between wild-type, heterozygous and homozygous mutant F2 rats, suggesting that this alteration may not be a significant determinant of hypertension in these rats on a chow diet. CONCLUSION: This study shows that the previously identified Gly583Cys change in Abcg5 in three hypertension-susceptible rats is responsible for the sitosterolemia, but may not be a major determinant of blood pressure in these rats.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
sitosterolemia susceptibilityISOAbcg5 (Rattus norvegicus)1598659; 1598659DNA:missense mutation: p.G583C , 1757G>T (rat)RGD 
sitosterolemia susceptibilityIAGP 1598659DNA:missense mutation: p.G583C , 1757G>T (rat)RGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
increased phytosterol level  IAGP 1598659DNA:missense mutation: p.G583C , 1757G>T ratRGD 
Objects Annotated

Genes (Rattus norvegicus)
Abcg5  (ATP binding cassette subfamily G member 5)

Genes (Mus musculus)
Abcg5  (ATP binding cassette subfamily G member 5)

Genes (Homo sapiens)
ABCG5  (ATP binding cassette subfamily G member 5)


Additional Information