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
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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