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

journal contribution
posted on 2023-05-16, 17:35 authored by Tonks, ID, Hacker, E, Irwin, N, Muller, HK, Keith, P, Mould, A, Zournazi, A, Pavey, S, Hayward, NK, Walker, G, Kay, GF
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.

History

Publication title

Pigment Cell Research

Volume

18

Issue

4

Pagination

252-264

ISSN

0893-5785

Department/School

Tasmanian School of Medicine

Publisher

Blackwell Munksgaard

Place of publication

Oxford, England

Repository Status

  • Restricted

Socio-economic Objectives

Clinical health not elsewhere classified

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