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  • Original Paper
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Loss of the LIM domain protein Lmo4 in the mammary gland during pregnancy impedes lobuloalveolar development

Oncogene volume 24, pages 4820–4828 (2005)Cite this article

Abstract

LMO4, a member of the LIM-only family of zinc-finger proteins, is overexpressed in a significant proportion of breast carcinomas and acts as a negative regulator of mammary epithelial differentiation. To delineate cell types within the developing mouse mammary gland that express Lmo4, we analysed different stages of mammopoiesis by immunohistochemistry. Lmo4 was found to be highly expressed in the proliferating cap cells of the terminal end bud and in the ductal and alveolar luminal cells of the mature mammary gland but was negligible or low in myoepithelial cells. To assess the physiological role of Lmo4 in the mammary gland, we generated conditionally targeted mice lacking Lmo4 in the mammary epithelium during pregnancy. Acute loss of Lmo4 in late pregnancy impaired lobuloalveolar development, accompanied by a two-fold reduction in the percentage of BrdU-positive cells. In contrast, germline loss of Lmo4 did not alter lobuloalveolar development arising from transplanted mammary anlagen, implying the existence of a compensatory mechanism in these knockout mice. Thus, the use of a conditional targeting strategy has revealed that Lmo4 is required for proper development of the mammary gland during pregnancy and indicated that Lmo4 acts as a positive regulator of alveolar epithelial proliferation.

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Acknowledgements

We are grateful to S Orkin for his generous gift of floxed Lmo4 mice. We wish to thank F Vaillant and G Robinson for invaluable advice and S Mihajlovic for histology. This work was supported by the Victorian Breast Cancer Research Consortium Inc. and the National Health and Medical Research Council (Australia).

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Authors and Affiliations

  1. The Walter and Eliza Hall Institute of Medical Research and Bone Marrow Research Laboratories, 1G Royal Parade, Parkville, 3050, VIC, Australia

    Eleanor Y M Sum, Mark Shackleton, Richard M Thomas, Lorraine A O'Reilly, Geoffrey J Lindeman & Jane E Visvader

  2. The Children's Hospital/Harvard Medical School, Boston, 02115, MA, USA

    Kyungmin Hahm

  3. University of Nebraska Medical Center, Omaha, 68198, NE, USA

    Kay-Uwe Wagner

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  1. Eleanor Y M Sum
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  2. Mark Shackleton
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  3. Kyungmin Hahm
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Correspondence to Jane E Visvader.

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Sum, E., Shackleton, M., Hahm, K. et al. Loss of the LIM domain protein Lmo4 in the mammary gland during pregnancy impedes lobuloalveolar development. Oncogene 24, 4820–4828 (2005). https://doi.org/10.1038/sj.onc.1208638

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