T antigen expression and tumorigenesis in transgenic mice containing a mouse major urinary protein/SV40 T antigen hybrid gene.
A hybrid mouse major urinary protein (MUP)/SV40 T antigen gene was microinjected into fertilized mouse embryos and the resulting transgenic mice analyzed for the regulated expression of the transgene. Available evidence indicates that the MUP gene used for the hybrid gene construct is expressed in both male and female liver and possibly mammary gland. Three different transgenic lines exhibited a consistent pattern of tissue specific expression of the transgene. As a consequence of transgene expression and T antigen synthesis in the liver, both male and female transgenic animals developed liver hyperplasia and tumors. Transgene expression and liver hyperplasia commenced at approximately 2-4 weeks of age, the same time that MUP gene expression is first detected in the liver. The expression of the transgene resulted in an immediate strong suppression of liver MUP mRNA levels but had relatively little effect on other liver specific mRNAs. From 4 to 8 weeks, the liver increased several fold in size, relative to non-transgenic littermates. Definitive tumor nodules were not apparent until 8-10 weeks. The transgene was also consistently found to be expressed in the skin sebaceous glands and the preputial gland, a modified sebaceous gland. The expression of the transgene in the skin sebaceous glands is consistent with the presence of MUP mRNA in the skin and a putative role for MUPs in the transport and excretion of small molecules. Occasional expression of the transgene in other tissues (kidney and mammary connective tissues) was also noted.(ABSTRACT TRUNCATED AT 250 WORDS)
Held
W A
WA
Roswell Park Memorial Institute, Department of Molecular and Cellular Biology, Buffalo, NY 14263.
Mullins
J J
JJ
Kuhn
N J
NJ
Gallagher
J F
JF
Gu
G D
GD
Gross
K W
KW
D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D005260:Female; D005813:Genes, Synthetic; D006965:Hyperplasia; D007668:Kidney / Q000032:analysis; D008099:Liver / Q000032:analysis / Q000473:pathology; D008107:Liver Diseases / Q000209:etiology / Q000235:genetics; D008114:Liver Neoplasms, Experimental / Q000209:etiology* / Q000235:genetics; D008297:Male; D008321:Mammary Glands, Animal / Q000032:analysis; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009374:Neoplasms, Experimental / Q000209:etiology / Q000235:genetics; D009928:Organ Specificity; D011230:Precancerous Conditions / Q000209:etiology / Q000235:genetics; D011506:Proteins / Q000235:genetics / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis*; D011994:Recombinant Proteins / Q000096:biosynthesis*; D012045:Regulatory Sequences, Nucleic Acid; D012627:Sebaceous Glands / Q000032:analysis
D000952:Antigens, Polyomavirus Transforming; D011506:Proteins; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; C035737:major urinary proteins