Dual loss of Rb1 and Trp53 in the adrenal medulla leads to spontaneous pheochromocytoma

Tonks, ID, Mould, AW, Schroder, WA, Cotterill, A, Hayward, NK, Walker, GJ and Kay, GF (2010) Dual loss of Rb1 and Trp53 in the adrenal medulla leads to spontaneous pheochromocytoma. Neoplasia, 12 3: 235-243. doi:10.1593/neo.91646

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Author Tonks, ID
Mould, AW
Schroder, WA
Cotterill, A
Hayward, NK
Walker, GJ
Kay, GF
Title Dual loss of Rb1 and Trp53 in the adrenal medulla leads to spontaneous pheochromocytoma
Journal name Neoplasia   Check publisher's open access policy
ISSN 1522-8002
1476-5586
Publication date 2010-03
Sub-type Article (original research)
DOI 10.1593/neo.91646
Open Access Status DOI
Volume 12
Issue 3
Start page 235
End page 243
Total pages 9
Place of publication Ann Arbor, MI, United States
Publisher Neoplasia Press
Collection year 2011
Language eng
Formatted abstract
Using a Cre/loxP system, we have determined the phenotypic consequences attributable to in vivo deletion of both Rb1 and Trp53 in the mouse adrenal medulla. The coablation of these two tumor suppressor genes during embryogenesis did not disrupt adrenal gland development but resulted in the neoplastic transformation of the neural crest-derived adrenal medulla, yielding pheochromocytomas (PCCs) that developed with complete penetrance and were inevitably bilateral. Despite their typically benign status, these PCCs had profound ramifications on mouse vitality, with effected mice having a median survival of only 121 days. Evaluation of these PCCs by both immunohistochemistry and electron microscopy revealed that most Rb1-/-:Trp53 -/- chromaffin cells possessed atypical chromagenic vesicles that did not seem capable of appropriately storing synthesized catecholamines. The structural remodeling of the heart in mice harboring Rb1-/-: Trp53-/- PCCs suggests that the mortality of these mice may be attributable to the inappropriate release of catecholamines from the mutated adrenal chromaffin cells. On the basis of the collective data from Rb1 and Trp53 knockout mouse models, it seems that the conversion of Rb1 loss-driven adrenal medulla hyperplasia to PCC can be greatly enhanced by the compound loss of Trp53, whereas the loss of Trp53 alone is generally ineffectual on adrenal chromaffin cell homeostasis. Consequently, the Trp53 tumor suppressor gene is an efficient genetic modifier of Rb1 loss in the development of PCC, and their compound loss in the adrenal medulla has a profound impact on both cellular homeostasis and animal vitality. Copyright © 2010 Neoplasia Press, Inc. All rights reserved.
Keyword Adrenal medulla
Animal cell
Animal experiment
Animal model
Animal tissue
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2011 Collection
School of Medicine Publications
 
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Created: Wed, 23 Mar 2011, 12:15:21 EST by Lisa Hennell on behalf of Medicine - Royal Brisbane and Women's Hospital