Pheochromocytomas and C-cell thyroid neoplasms in transgenic c-mos mice: a model for the human multiple endocrine neoplasia type 2 syndrome.
Transgenic mice carrying and expressing a mos protooncogene, linked to the Moloney murine sarcoma virus long terminal repeat, develop severe neurological defects and lens abnormalities. Here we report that after long latent periods, mice in three of four of these mos transgenic lines develop a high frequency of multicentric pheochromocytomas and/or medullary thyroid neoplasms. The pattern of tumor formation is remarkably similar to the human autosomal dominantly inherited neoplastic syndrome, multiple endocrine neoplasia type 2 (MEN 2), and tumors from these transgenic animals display the same neuroendocrine marker staining pattern as seen in MEN 2. The similarity between the tumor pathologies and presentation patterns of MEN 2 patients and mos transgenic mice suggests that they may arise through related pathways. The type of tumor presentation varies in a line-dependent manner indicating that there is interaction between the transgene and the genetic background. Moreover, when the non-tumor-bearing mos transgenic line is crossed to a different mouse background, the F1 offspring display the MEN 2 phenotype. These studies indicate that penetrance of the autosomal dominant mos transgenic phenotype is dependent on both integration site and background.
ABL-Basic Research Program, NCI-Frederick Cancer Research and Development Center, Maryland 21701.
N
N
Schulz
F
F
Propst
M P
MP
Rosenberg
R I
RI
Linnoila
R S
RS
Paules
R
R
Kovatch
Y
Y
Ogiso
G
G
Vande Woude
D000310:Adrenal Gland Neoplasms / Q000235:genetics; D000818:Animals; D015152:Blotting, Northern; D004195:Disease Models, Animal; D015870:Gene Expression; D016258:Genes, mos; D051379:Mice; D008822:Mice, Transgenic; D009377:Multiple Endocrine Neoplasia / Q000235:genetics*; D009374:Neoplasms, Experimental / Q000473:pathology*; D010673:Pheochromocytoma / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D013964:Thyroid Neoplasms / Q000235:genetics*
D012333:RNA, Messenger