Neuropathology of genetically engineered mice: consensus report and recommendations from an international forum.
The Mouse Models of Cancer Consortium of the NCI sponsored a meeting of neuropathologists and veterinary pathologists in New York City in November of 2000. A rapidly growing number of genetically engineered mice (GEM) predisposed to tumors of the nervous system have led to a concomitant need for neuropathological evaluation and validation of these models. A panel of 13 pathologists reviewed material representing most of the available published and unpublished GEM models of medulloblastoma, primitive neuroectodermal tumor, astrocytoma, oligodendroglioma, mixed glioma, and tumors of the peripheral nerve. The GEM tumors were found to have many similarities and some distinct differences with respect to human disease. After review of the biology and pathology for all models presented, participants were split into groups reflective of clinical expertise in human pathology, tumor biology, neuroimaging, or treatment/intervention. Recommendations were made detailing an extensive and complete neuropathological characterization of animals. Importance was placed on including information on strains, tumor clonality, and examination for genetic mutation or altered gene expression characteristics of the corresponding human malignancy. Specific proposals were made to incorporate GEM models in emerging neuroradiological modalities. Recommendations were also made for preclinical validation of these models in cancer therapeutics, and for incorporation of surrogate markers of tumor burden to facilitate preclinical evaluation of new therapies.
Weiss
William A
WA
Department of Neurology, University of California, 521 Parnassus Avenue, San Francisco, California, CA 94143-0114, USA. weiss@cgl.ucsf.edu
Israel
Mark
M
Cobbs
Charles
C
Holland
Eric
E
James
C David
CD
Louis
David N
DN
Marks
Cheryl
C
McClatchey
Andrea I
AI
Roberts
Tim
T
Van Dyke
Terry
T
Wetmore
Cynthia
C
Chiu
Ing-Ming
IM
Giovannini
Marco
M
Guha
Abhijit
A
Higgins
Robert J
RJ
Marino
Silvia
S
Radovanovic
Ivan
I
Reilly
Karlyne
K
Aldape
Ken
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D000818:Animals; D005818:Genetic Engineering; D051379:Mice; D009423:Nervous System Neoplasms / Q000235:genetics* / Q000473:pathology