Transgenic overexpression of p23 induces spontaneous hydronephrosis in mice

Summary p23 is a cochaperone of heat shock protein 90 and also interacts functionally with numerous steroid receptors and kinases. However, the in vivo roles of p23 remain unclear. To explore its in vivo function, we generated the transgenic (TG) mice ubiquitously overexpressing p23. The p23 TG mice...

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Published in:International journal of experimental pathology 2011-08, Vol.92 (4), p.251-259
Main Authors: Lee, Jaehoon, Kim, Hye Jin, Moon, Jung Ah, Sung, Young Hoon, Baek, In-Jeoung, Roh, Jae-il, Ha, Na Young, Kim, Seung-Yeon, Bahk, Young Yil, Lee, Jong Eun, Yoo, Tae Hyun, Lee, Han-Woong
Format: Article
Language:English
Subjects:
Animals
Aryl Hydrocarbon Hydroxylases - metabolism
aryl hydrocarbon receptor
Aryl hydrocarbon receptors
Cytochrome P-450 CYP1A1 - metabolism
Cytochrome P-450 CYP1B1
Cytochrome P450
Disease Models, Animal
Female
Gene Expression Regulation - physiology
Heat shock proteins
Hsp90 protein
hydronephrosis
Hydronephrosis - metabolism
Hydronephrosis - physiopathology
Intramolecular Oxidoreductases - genetics
Intramolecular Oxidoreductases - physiology
kidney
Kidney - metabolism
Kidney - physiopathology
Male
Mice
Mice, Transgenic
Original
p23
Prostaglandin-E Synthases
Receptors, Aryl Hydrocarbon - metabolism
Signal Transduction - physiology
Steroid hormone receptors
TG mouse
Transgenic mice
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Summary:Summary p23 is a cochaperone of heat shock protein 90 and also interacts functionally with numerous steroid receptors and kinases. However, the in vivo roles of p23 remain unclear. To explore its in vivo function, we generated the transgenic (TG) mice ubiquitously overexpressing p23. The p23 TG mice spontaneously developed kidney abnormalities closely resembling human hydronephrosis. Consistently, kidney functions deteriorate significantly in the p23 TG mice compared to their wild‐type (WT) littermates. Furthermore, the expression of target genes for aryl hydrocarbon receptor (AhR), such as cytochrome P450, family 1, subfamily A, polypeptide 1 (Cyp1A1) and cytochrome P450, family 1, subfamily B, polypeptide 1 (Cyp1B1), were induced in the kidneys of the p23 TG mice. These results indicate that the overexpression of p23 contributes to the development of hydronephrosis through the upregulation of the AhR pathway in vivo.
ISSN:0959-9673
1365-2613
DOI:10.1111/j.1365-2613.2011.00762.x