Melanocytes in conditional Rb–/– mice are normal in vivo but exhibit proliferation and pigmentation defects in vitro

Tonks, Ian D., Hacker, Elke, Irwin, Nicole, Muller, H. Conrad, Keith, Patricia, Mould, Arne, Zournazi, Anna, Pavey, Sandra, Hayward, Nicholas K., Walker, Graeme and Kay, Graham F. (2005) Melanocytes in conditional Rb–/– mice are normal in vivo but exhibit proliferation and pigmentation defects in vitro. Pigment Cell and Melanoma Research, 18 4: 252-264. doi:10.1111/j.1600-0749.2005.00245.x

Author Tonks, Ian D.
Hacker, Elke
Irwin, Nicole
Muller, H. Conrad
Keith, Patricia
Mould, Arne
Zournazi, Anna
Pavey, Sandra
Hayward, Nicholas K.
Walker, Graeme
Kay, Graham F.
Title Melanocytes in conditional Rb–/– mice are normal in vivo but exhibit proliferation and pigmentation defects in vitro
Journal name Pigment Cell and Melanoma Research   Check publisher's open access policy
ISSN 0893-5785
Publication date 2005-08
Sub-type Article (original research)
DOI 10.1111/j.1600-0749.2005.00245.x
Volume 18
Issue 4
Start page 252
End page 264
Total pages 13
Place of publication Malden, MA, United States
Publisher Wiley-Blackwell Publishing
Language eng
Subject 111201 Cancer Cell Biology
111203 Cancer Genetics
110304 Dermatology
Formatted abstract
The function of the retinoblastoma tumour suppressor (Rb1), and the pocket protein family in general, has been implicated as an important focal point for deregulation in many of the molecular pathways mutated in melanoma. We have focused on the role of Rb1 in mouse melanocyte homeostasis using gene targeting and Cre/loxP mediated tissue-specific deletion. We show that constitutive Cre-mediated ablation of Rb1 exon 2 prevents the production of Rb1 and recapitulates the phenotype encountered in other Rb1 knockout mouse models. Mice with conditional melanocyte-specific ablation of Rb1 manifest overtly normal pigmentation and are bereft of melanocytic hyperproliferative defects or apoptosis-induced depigmentation. Histologically, these mice have melanocyte morphology and distribution comparable with control littermates. In contrast, Rb1-null melanocytes removed from their in vivo micro-environment and cultured in vitro display some of the characteristics associated with a transformed phenotype. They proliferate at a heightened rate when compared with control melanocytes and have a decreased requirement for mitogens. With progressive culture the cells depigment at relatively early passage and display a gross morphology which, whilst reminiscent of early passage melanocytes, is generally different to equivalent passage control cells. These results indicate that Rb1 is dispensable for in vivo melanocyte homeostasis when its ablation is targeted from the melanoblast stage onwards, however, when cultured in vitro, Rb1 loss increases melanocyte growth but the cells are not fully transformed
Keyword Retinoblastoma
Conditional deletion
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
School of Medicine Publications
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Citation counts: TR Web of Science Citation Count  Cited 14 times in Thomson Reuters Web of Science Article | Citations
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Created: Thu, 12 Feb 2009, 15:47:52 EST by Maryanne Watson on behalf of Medicine - Royal Brisbane and Women's Hospital