The chimeric gene linked to glucocorticoid-suppressible hyperaldosteronism encodes a fused P-450 protein prssessing aldosterone synthase activity
Glucocorticoid-suppressible hyperaldosteronism (GSH) is one variety of primary aldosteronism with hypertension and is inherited in an autosomal dominant mode. A recent report has indicated that GSH is caused by a gene duplication arising from unequal crossing over between the two genes, CYP11B1 and...
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Published in | Biochemical and biophysical research communications Vol. 189; no. 2; pp. 885 - 891 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
Elsevier Inc
15.12.1992
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Subjects | |
Online Access | Get full text |
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Summary: | Glucocorticoid-suppressible hyperaldosteronism (GSH) is one variety of primary aldosteronism with hypertension and is inherited in an autosomal dominant mode. A recent report has indicated that GSH is caused by a gene duplication arising from unequal crossing over between the two genes,
CYP11B1 and
CYP11B2, encoding P-450
11β and P-450
C18, respectively (
Lifton et al.
Nature (1992)
355, 262–265). The nucleotide sequence analysis in the present study has demonstrated that unequal crossing over in the chimeric gene formed by the gene duplication occurs within the region from the 3′-portion of exon 4 through the 5′-portion of intron 4 in Australian GSH patients. Namely, the chimeric gene encodes a fused P-450 protein consisting of the amino-terminal side of P-450
11β (encoded by exons 1–4 of
CYP11B1) and the carboxyl-terminal side of P-450
C18 (encoded by exons 5–9 of
CYP11B2). When a cDNA corresponding to the chimeric gene is transfected into COS-7 cells, the fused P-450 protein expressed in the mitochondria exhibits steroid 18-hydroxylase or aldosterone synthase activity. These results provide the molecular genetic basis for the characteristic biochemical phenotype of GSH patients. |
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ISSN: | 0006-291X 1090-2104 |
DOI: | 10.1016/0006-291X(92)92286-7 |