TY - JOUR
T1 - From Nf1 to Sdhb knockout
T2 - Successes and failures in the quest for animal models of pheochromocytoma
AU - Lepoutre-Lussey, Charlotte
AU - Thibault, Constance
AU - Buffet, Alexandre
AU - Morin, Aurélie
AU - Badoual, Cécile
AU - Bénit, Paule
AU - Rustin, Pierre
AU - Ottolenghi, Chris
AU - Janin, Maxime
AU - Castro-Vega, Luis Jaime
AU - Trapman, Jan
AU - Gimenez-Roqueplo, Anne Paule
AU - Favier, Judith
N1 - Publisher Copyright:
© 2015 Elsevier Ireland Ltd.
PY - 2016/2/5
Y1 - 2016/2/5
N2 - Pheochromocytomas and paragangliomas (PPGL) are rare neuroendocrine tumors characterized by a high frequency of hereditary forms. Based on transcriptome classification, PPGL can be classified in two different clusters. Cluster 1 tumors are caused by mutations in SDHx, VHL and FH genes and are characterized by a pseudohypoxic signature. Cluster 2 PPGL carry mutations in RET, NF1, MAX or TMEM127 genes and display an activation of the MAPK and mTOR signaling pathways. Many genetically engineered and allografted mouse models have been generated these past 30 years to investigate the mechanisms of PPGL tumorigenesis and test new therapeutic strategies. Among them, only Cluster 2-related models have been successful while no Cluster 1-related knockout mouse was so far reported to develop a PPGL. In this review, we present an overview of existing, successful or not, PPGL models, and a description of our own experience on the quest of Sdhb knockout mouse models of PPGL.
AB - Pheochromocytomas and paragangliomas (PPGL) are rare neuroendocrine tumors characterized by a high frequency of hereditary forms. Based on transcriptome classification, PPGL can be classified in two different clusters. Cluster 1 tumors are caused by mutations in SDHx, VHL and FH genes and are characterized by a pseudohypoxic signature. Cluster 2 PPGL carry mutations in RET, NF1, MAX or TMEM127 genes and display an activation of the MAPK and mTOR signaling pathways. Many genetically engineered and allografted mouse models have been generated these past 30 years to investigate the mechanisms of PPGL tumorigenesis and test new therapeutic strategies. Among them, only Cluster 2-related models have been successful while no Cluster 1-related knockout mouse was so far reported to develop a PPGL. In this review, we present an overview of existing, successful or not, PPGL models, and a description of our own experience on the quest of Sdhb knockout mouse models of PPGL.
KW - Chromaffin cells
KW - Genetically engineered mouse
KW - Knockout
KW - Pheochromocytoma
KW - Xenograft
UR - http://www.scopus.com/inward/record.url?scp=84953639348&partnerID=8YFLogxK
U2 - 10.1016/j.mce.2015.06.027
DO - 10.1016/j.mce.2015.06.027
M3 - Article
C2 - 26123588
AN - SCOPUS:84953639348
SN - 0303-7207
VL - 421
SP - 40
EP - 48
JO - Molecular and Cellular Endocrinology
JF - Molecular and Cellular Endocrinology
ER -