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Melanocytes in conditional Rb-/- mice are normal in vivo but exhibit proliferation and pigmentation defects in vitro
Citation
Tonks, ID and Hacker, E and Irwin, N and Muller, HK and Keith, P and Mould, A and Zournazi, A and Pavey, S and Hayward, NK and Walker, G and Kay, GF, Melanocytes in conditional Rb-/- mice are normal in vivo but exhibit proliferation and pigmentation defects in vitro, Pigment Cell Research, 18, (4) pp. 252-264. ISSN 0893-5785 (2005) [Refereed Article]
DOI: doi:10.1111/j.1600-0749.2005.00245.x
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. Copyright © Blackwell Munksgaard 2005.
Item Details
| Item Type: | Refereed Article |
|---|---|
| Research Division: | Biomedical and Clinical Sciences |
| Research Group: | Oncology and carcinogenesis |
| Research Field: | Oncology and carcinogenesis not elsewhere classified |
| Objective Division: | Health |
| Objective Group: | Clinical health |
| Objective Field: | Clinical health not elsewhere classified |
| UTAS Author: | Muller, HK (Professor Konrad Muller) |
| ID Code: | 38603 |
| Year Published: | 2005 |
| Web of Science® Times Cited: | 16 |
| Deposited By: | Pathology |
| Deposited On: | 2005-08-01 |
| Last Modified: | 2006-05-05 |
| Downloads: | 0 |
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