The expression of a metallothionein-ovine growth hormone fusion gene in transgenic mice does not impair fertility but results in pathological lesions in the liver.
The physiological effects of high serum levels of ovine GH (oGH) were studied in three generations of transgenic mice carrying a metallothionein 1-(MT)oGH fusion gene. Livers of mice expressing oGH were enlarged, irrespective of the level of serum oGH detected. In mice expressing high levels of oGH, direct measurements of hepatocytes in liver sections revealed that cell and nuclear size were abnormally large. Hepatocytes of different transgenic mice varied from 1.4-2.2 times normal size and hepatocyte nuclei varied from 1.7-2.4 times normal size. In addition, intranuclear inclusions were observed in hepatocytes of transgenic mice and their presence was always associated with high serum levels of oGH. In contrast to female transgenic mice containing mouse MT-human, rat, or bovine GH fusion genes female mice containing the MT oGH fusion gene were fertile and their pituitary glands showed synthesis of GH.
Orian
J M
JM
Department of Veterinary Preclinical Sciences, University of Melbourne, Parkville, Victoria, Australia.
Lee
C S
CS
Weiss
L M
LM
Brandon
M R
MR
D000818:Animals; D015152:Blotting, Northern; D002467:Cell Nucleus / Q000648:ultrastructure; D003001:Cloning, Molecular; D005260:Female; D005298:Fertility; D005786:Gene Expression Regulation; D013006:Growth Hormone / Q000235:genetics / Q000502:physiology*; D007124:Immunoenzyme Techniques; D008099:Liver / Q000473:pathology / Q000648:ultrastructure*; D008297:Male; D008668:Metallothionein / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008854:Microscopy, Electron; D010902:Pituitary Gland / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012756:Sheep
D012333:RNA, Messenger; D013006:Growth Hormone; D008668:Metallothionein