Mouse model of congenital polycythemia: Homologous replacement of murine gene by mutant human erythropoietin receptor gene.

Content Provider	Semantic Scholar
Author	Divoky, Vladimir Liu, Zhonghua Ryan, Timothy M. Prchal, Jaroslav Townes, Tim M. Prchal, Josef T.
Copyright Year	2001
Abstract	Mutations causing truncations of the cytoplasmic domain of the human erythropoietin receptor (EPOR) result in a dominantly inherited disorder-primary familial congenital polycythemia. This disorder is characterized by increased numbers of erythrocytes (polycythemia) and by in vitro hypersensitivity of erythroid precursors to erythropoietin. The consequences of EPOR truncation in nonerythroid tissues are unknown. We replaced the murine EPOR gene with a wild-type human EPOR gene and a mutant human EPOR gene that we initially identified in a patient with polycythemia. This mutation leads to an EPOR truncated after the first tyrosine residue of the intracellular domain. Mice heterozygous for this mutant allele and a wild-type human EPOR allele mimicked the human disorder. Interestingly, mice that were homozygous for the mutant human allele were severely polycythemic but viable. Our results provide a model for functional studies of EPOR-triggered signaling pathways in erythropoiesis. These animals can now be used to investigate the molecular pathophysiology of this gain-of-function EPOR mutation in erythroid tissue and in those nonerythroid tissues that express EPOR.
File Format	PDF HTM / HTML
DOI	10.1073/pnas.98.3.986
PubMed reference number	11158582
Journal	Medline
Volume Number	98
Issue Number	3
Alternate Webpage(s)	http://www.pnas.org/content/98/3/986.full.pdf
Alternate Webpage(s)	https://doi.org/10.1073/pnas.98.3.986
Journal	Proceedings of the National Academy of Sciences of the United States of America
Language	English
Access Restriction	Open
Content Type	Text
Resource Type	Article