Coordinate regulation of 11 beta-HSD and Ke 6 genes in cpk mouse: implications for steroid metabolic defect in PKD
Autor: | B. M. Brenner, N. Aziz, M. M. Maxwell |
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Rok vydání: | 1994 |
Předmět: |
medicine.medical_specialty
Transcription Genetic Physiology Molecular Sequence Data Regulatory Sequences Nucleic Acid Kidney Major histocompatibility complex Gene Expression Regulation Enzymologic Homology (biology) Conserved sequence Major Histocompatibility Complex Mice Histocompatibility Antigens Internal medicine Consensus Sequence medicine Polycystic kidney disease Animals Humans Amino Acid Sequence RNA Messenger Glucocorticoids Gene Psychological repression Conserved Sequence Mammals Regulation of gene expression Polycystic Kidney Diseases Base Sequence Sequence Homology Amino Acid biology Genetic Carrier Screening Hydroxysteroid Dehydrogenases Blotting Northern medicine.disease Mice Mutant Strains Rats Cell biology Endocrinology medicine.anatomical_structure Gene Expression Regulation Liver Mice Inbred DBA Hydroxyprostaglandin Dehydrogenases biology.protein 11-beta-Hydroxysteroid Dehydrogenases Steroids Oxidoreductases |
Zdroj: | American Journal of Physiology-Renal Physiology. 267:F791-F797 |
ISSN: | 1522-1466 1931-857X |
Popis: | Polycystic kidney disease (PKD) is characterized by multiple renal cysts, which ultimately result in renal failure. We have reported the identification of a new gene, Ke 6, within the major histocompatibility complex, which is downregulated in two different mouse models of heritable PKD (N. Aziz, M. Maxwell, B. St.-Jacques, and B.M. Brenner. Mol. Cell. Biol. 13: 1847-1853, 1993). The Ke 6 gene gives rise to two transcripts, Ke 6a and Ke 6b. Ke 6a protein has significant homology to several mammalian and bacterial steroid dehydrogenases. The homology of Ke 6a protein to specific functional domains of the human and rat 11 beta-hydroxysteroid dehydrogenase enzyme (11 beta-HSD), which inactivates glucocorticoids, is substantial. We report here that the Ke 6 gene and the 11 beta-HSD gene are regulated in the same aberrant pattern in the cpk mouse. The strong evidence for a critical role of steroids in cystogenesis leads us to propose that a possible elevation of intrahepatic and intrarenal steroid levels occurs in the cpk mouse as a result of repression of steroid metabolic enzymes, which ultimately leads to development of cysts. |
Databáze: | OpenAIRE |
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