18 transgene, 3 males showed enlarged seminal 
vesicles evident by 50 wk of age. One of these ani- 
mals was bred, and a line has been established. Sur- 
prisingly, one female in the Gl generation devel- 
oped a cervical tumor, evident at —62 wk of age. 
Transgenic males and females in this line will be 
used to identify and characterize secondary events 
that lead to this transformation. 
B. Pancreatic cancer. A mouse model for pancre- 
atic acinar cell tumorigenesis has been derived by 
targeting the expression of the SV40 T antigen gene 
in transgenic mice by utilizing the rat trypsin I 
5 '-flanking DNA. The development of this tumor in 
mice bearing this construct is a multistep process 
that begins with pancreatic hyperplasia (evident be- 
PUBLICATIONS 
fore birth), which progresses to dysplasia and the 
formation of multiple large tumor nodules by 2-4 
months of age. T antigen alone appears sufficient to 
induce hyperplasia, because all cells are affected 
similarly, and the effect occurs as early in develop- 
ment as T antigen can be detected. Because T anti- 
gen-induced hyperplasia rarely progresses to form 
tumors, other secondary events that complement 
or augment T antigen action must be required. 
Transgenic mice that reproducibly develop pancre- 
atic adenocarcinoma should permit the identifica- 
tion of these secondary genetic events. 
Dr. Hammer is Assistant Professor of Cell Biology 
and Neuroscience at the University of Texas South- 
western Medical Center at Dallas. 
Articles 
Carroll, R.J., Hammer, R.E., Chan, S.J., Swift, H.H., Rubenstein, A.H., and Steiner, D.F. 1988. A mutant human 
proinsulin is secreted from islets of Langerhans in increased amounts via an unregulated pathway. Proc 
Natl Acad Sci USA 85:8943-8947. 
Mathews, L.S. , Hammer, R.E. , Behringer, R.R. , D'Ercole, J., Bell, G.I. , Brinster, R.L., and Palmiter, R.D. 1988. 
Growth enhancement of transgenic mice expressing human insulin-like growth factor I. Endocrinology 
123:2827-2833. 
Miller, K.E, Bolt, D.J., Pursel, VG., Hammer, R.E. , Pinkert, C.A., Palmiter, R.D. , and Brinster, R.L. 1989. Expres- 
sion of human or bovine growth hormone gene with a mouse metallothionein-1 promoter in transgenic 
swine alters the secretion of porcine growth hormone and insulin-like growth factor-I. / Endocrinol 
120:481-488. 
Pursel, VG., Pinkert, C.A., Miller, K.E, Bolt, D.J., Campbell, R.G., Palmiter, R.D. , Brinster, R.L., and Hammer, 
R.E. 1989. Genetic engineering of livestock. Science 244:1281-1288. 
Quaife, C.J., Mathews, L.S., Pinkert, C.A., Hammer, R.E., Brinster, R.L., and Palmiter, R.D. 1989. Histopathol- 
ogy associated with elevated levels of growth hormone and insulin-like growth factor I in transgenic mice. 
Endocrinology 124:40-48. 
Rexroad, C.E., Hammer, R.E. , Bolt, D.J., Mayo, K.E., Frohman, L.A., Palmiter, R.D. , and Brinster, R.L. 1989. 
Production of transgenic sheep with growth-regulating genes. Mol Reprod Dev 1:164-169. 
Swift, G.H., Kruse, R, MacDonald, R.J., and Hammer, R.E. 1989. Differential requirements for cell-specific 
elastase I enhancer domains in transfected cells and transgenic mice. Genes Dev 3:687-696. 
Taurog, J.D., Durand, J.P, el-Zaatari, F.A., and Hammer, R.E. 1988. Studies of HLA-B27-associated disease. Am 
/Me^ 85:59-60. 
Taurog, J.D., Lowen, L., Forman, J., and Hammer, R.E. 1989. HLA-B27 in inbred and non-inbred transgenic 
mice. Cell surface expression and recognition as an alloantigen in the absence of human p2-microglobulin. 
J Immunol 141:4020-4023. 
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