The Smo/Smo model: Hedgehog-induced medulloblastoma with 90% incidence and leptomeningeal spread

Hatton, Beryl A., Villavicencio, Elisabeth H., Tsuchiya, Karen D., Pritchard, Joel I., Ditzler, Sally, Pullar, Barbara, Hansen, Stacey, Knoblaugh, Sue E., Lee, Donghoon, Eberhart, Charles G., Hallahan, Andrew R. and Olson, James M. (2008) The Smo/Smo model: Hedgehog-induced medulloblastoma with 90% incidence and leptomeningeal spread. Cancer Research, 68 6: 1768-1776. doi:10.1158/0008-5472.CAN-07-5092


Author Hatton, Beryl A.
Villavicencio, Elisabeth H.
Tsuchiya, Karen D.
Pritchard, Joel I.
Ditzler, Sally
Pullar, Barbara
Hansen, Stacey
Knoblaugh, Sue E.
Lee, Donghoon
Eberhart, Charles G.
Hallahan, Andrew R.
Olson, James M.
Title The Smo/Smo model: Hedgehog-induced medulloblastoma with 90% incidence and leptomeningeal spread
Journal name Cancer Research   Check publisher's open access policy
ISSN 0008-5472
1538-7445
Publication date 2008-03-15
Sub-type Article (original research)
DOI 10.1158/0008-5472.CAN-07-5092
Volume 68
Issue 6
Start page 1768
End page 1776
Total pages 9
Editor F. J. Rauscher III
Place of publication Philadelphia, Pennsylvania, U.S.A.
Publisher American Association for Cancer Research
Language eng
Subject 11 Medical and Health Sciences
1112 Oncology and Carcinogenesis
Formatted abstract
Toward the goal of generating a mouse medulloblastoma model with increased tumor incidence, we developed a homozygous version of our ND2:SmoA1model. Medulloblastomas form in 94% of homozygous Smo/Smo mice by 2 months of age. Tumor formation is, thus, predictable by age, before the symptomatic appearance of larger lesions. This high incidence and early onset of tumors is ideal for preclinical studies because mice can be enrolled before symptom onset and with a greater latency period before late-stage disease. Smo/Smo tumors also display leptomeningeal dissemination of neoplastic cells to the brain and spine, which occurs in many human cases. Despite an extended proliferation of granule neuron precursors (GNP) in the postnatal external granular layer (EGL), the internal granular layer formed normally in Smo/Smo mice and tumor formation occurred only in localized foci on the superficial surface of the molecular layer. Thus, tumor formation is not simply the result of over proliferation of GNPs within the EGL. Moreover, Smo/Smo medulloblastomas were transplantable and serially passaged in vivo, demonstrating the aggressiveness of tumor cells and their transformation beyond a hyperplastic state. The Smo/Smo model is the first mouse medulloblastoma model to show leptomeningeal spread. The adherence to human pathology, high incidence, and early onset of tumors thus make Smo/Smo mice an efficient model for preclinical studies.
© 2008 American Association for Cancer Research.
Keyword Granule neuron precursors
Medulloblastoma
Leptomeningeal spread
Sonic hedgehog
Cerebellum
Mouse cancer models
Q-Index Code C1
Q-Index Status Provisional Code

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
School of Medicine Publications
 
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Created: Thu, 03 Sep 2009, 10:23:43 EST by Mr Andrew Martlew on behalf of Faculty Of Health Sciences