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Susceptibility to NF1-associated pheochromocytoma is modified in females by Pheom1 on mouse chromosome 16

Wednesday, October 10, 2012 — Poster Session II

Noon – 2:00 p.m

Natcher Conference Center, Building 45



* FARE Award Winner


  • G.N. Jones
  • J.C. Van-Schaick
  • S. Kim
  • T. Huynh
  • U. Shankavaram
  • K. Pacak
  • K.W. Broman
  • K.M. Reilly


Pheochromocytoma (pheo) is a rare adrenal medullary tumor that can occur in conjunction with several familial tumor syndromes including Neurofibromatosis type I (NF1). We previously reported adrenal tumors in the NPcis mouse model for NF1, albeit with limited characterization. Here, we provide more detailed characterization of the NPcis adrenal tumors and demonstrate altered risk to pheo where inbred NPcis females on the C57BL/6J (B6) background were more susceptible to pheo than their male siblings. Moreover, B6-NPcis females were significantly more prone to adrenal tumors than 129S4/SvJae (129) NPcis females, revealing strain and sex specificity. Backcross mapping and binary trait linkage analysis of 129x(B6x129)-NPcis animals revealed a female-specific linkage peak on distal chromosome 16 that we named Pheochromocytoma modifier 1 (Pheom1). Female susceptibility to pheo was significantly altered in response to variations in the background genotype of Pheom1, whereas males were not affected by Pheom1. Interestingly, Pheom1 overlaps the mouse Ts65Dn locus (syntenic with the human Down Syndrome region) which was reported to cause increased susceptibility to adrenal tumors in female Ts65Dn;NPcis mice, further supporting our conclusion that Pheom1 modulates female risk to pheo. Overall, these data indicate sex and strain specific modifiers in Pheom1 dictate susceptibility to adrenal medullary tumorigenesis.

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