TY - JOUR
T1 - Abnormal regulation of the Ke 6 gene, a new 17β-hydroxysteroid dehydrogenase in the cpk mouse kidney
AU - Ramirez, Sylvia
AU - Fomitcheva, Ioulia
AU - Aziz, Nazneen
N1 - Funding Information:
We thank Monica Ailawadi for superb technical assistance in the early part of the study. We are grateful to Dr Adam Sun (University of Rhode Island Hospital) for providing the CTA cells and Dr Van Cherington (Tufts University) for gift of the ϕ2TEXS5 cells. This work was supported by grants form the NIDDK (R-01) and March of Dimes Birth Defects Foundation to N.A.
PY - 1998/8/25
Y1 - 1998/8/25
N2 - The function encoded by the Ke 6 gene has been recently determined to be 17β-hydroxysteroid dehydrogenase. Previously, the abnormal expression of the Ke 6 gene has been intimately associated with development of recessive polycystic kidney disease. The Ke 6 gene is normally expressed at very high levels in the kidney and liver and is severely down regulated in all recessive murine models of polycystic kidney disease that have been examined to date. Here, we report a detailed examination of the promoter region of the Ke 6 gene in normal mouse kidney cells (CTA) and in cells derived from mouse kidneys homozygous for the cpk (congenital polycystic kidney) mutation, using transfection analysis and DNA-protein gel shift assays. The minimal promoter region, P1 (+1 to -96), and a putative enhancer site, P3 (-165 to -256), within the Ke 6 gene 5' flanking sequence have been identified. We have also identified another region, P2 (-97 to -165), that may be responsible for the lower promoter activity of the Ke 6 gene in cpk cells, Furthermore, absence of binding of a 38 kDa nuclear protein to a 16 bp sequence element (PIA) within the minimal promoter of the Ke 6 gene suggests that the P1A element could be responsible for the overall reduction in promoter function in cpk cells.
AB - The function encoded by the Ke 6 gene has been recently determined to be 17β-hydroxysteroid dehydrogenase. Previously, the abnormal expression of the Ke 6 gene has been intimately associated with development of recessive polycystic kidney disease. The Ke 6 gene is normally expressed at very high levels in the kidney and liver and is severely down regulated in all recessive murine models of polycystic kidney disease that have been examined to date. Here, we report a detailed examination of the promoter region of the Ke 6 gene in normal mouse kidney cells (CTA) and in cells derived from mouse kidneys homozygous for the cpk (congenital polycystic kidney) mutation, using transfection analysis and DNA-protein gel shift assays. The minimal promoter region, P1 (+1 to -96), and a putative enhancer site, P3 (-165 to -256), within the Ke 6 gene 5' flanking sequence have been identified. We have also identified another region, P2 (-97 to -165), that may be responsible for the lower promoter activity of the Ke 6 gene in cpk cells, Furthermore, absence of binding of a 38 kDa nuclear protein to a 16 bp sequence element (PIA) within the minimal promoter of the Ke 6 gene suggests that the P1A element could be responsible for the overall reduction in promoter function in cpk cells.
KW - Ke 6 gene
KW - Promoter activity
KW - cpk cells
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U2 - 10.1016/S0303-7207(98)00143-9
DO - 10.1016/S0303-7207(98)00143-9
M3 - Article
C2 - 9806346
AN - SCOPUS:0032566362
SN - 0303-7207
VL - 143
SP - 9
EP - 22
JO - Molecular and Cellular Endocrinology
JF - Molecular and Cellular Endocrinology
IS - 1-2
ER -