Human erythropoietin induces lung failure and erythrocytosis in transgenic mice.
We have expressed human erythropoietin (EPO) in transgenic mice using a recombinant EPO cDNA combined with a partial TPO construct. The gene was microinjected using standard techniques and five mice were detected as transgenic by PCR and further used as founders. The life span of the transgenic founders was much shorter than that of their normal littermates. Most of the tissues of the transgenic founders contained human EPO transcripts as judged by RT-PCR. Especially high expression levels were seen in the liver and lung. EPO protein levels in serum were examined by ELISA and ranged from 266, 414 mIU/ml. The number of red blood cell, white blood cell and hemoglobin in the hEPO transgenic mice was higher than in normal mice. These results indicate that overexpression of hEPO is deleterious and can provoke lung failure and erythrocytosis.
Kim
Myoung Ok
MO
School of Life Sciences and Biotechnology, College of Natural Sciences, Kyungpook National University, Daegu 702-701, Korea.
Kim
Sung Hyun
SH
Shin
Mi Jung
MJ
Lee
Dong Beom
DB
Kim
Tae Won
TW
Kim
Kil Soo
KS
Ha
Ji Hong
JH
Lee
Sanggyu
S
Park
Yong Bok
YB
Kim
Sun Jung
SJ
Ryoo
Zae Young
ZY
D000818:Animals; D001772:Blood Cell Count; D002417:Cattle; D002452:Cell Count; D004921:Erythropoietin / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D008171:Lung Diseases / Q000139:chemically induced / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010375:Pedigree; D011086:Polycythemia / Q000139:chemically induced / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins; D019076:Transgenes
D012333:RNA, Messenger; D011994:Recombinant Proteins; D004921:Erythropoietin