8 
£*:. Gorovitz asked whether substances such as restriction enzymes are introduced 
into the embryos during microinjection. Dr. Scangos replied that only the 
foreign DNA is injected into the embryos. 
!>:. Scangos said transgenic mice usually express fb reign genes in a tissue 
specific pattern. The factors regulating tissue specific expression are not 
understood, although expression appears to depend on the site of chromosomal 
insertion with overall regulation of expression determining in vhich tissues 
the genes will be expressed. Chromosomal domains appear to have an effect on 
the level, but do not appear to affect tissue specific expression. It appears 
that a 200 base pair seguence contiguous with the promotor at the 5' end of 
the rat elastase 1 gene directs expression specifically to pancreatic tissue. 
Dr. Scangos offered some examples of microinjected foreign genes which were 
expressed in a tissue specific pattern; the rat elastase 1 gene was expressed 
in pancreatic acinar cells; the human beta-globin gene was expressed in erythroid 
cells; a mouse/human beta-globin hybrid gene was expressed in erythroid cells; 
the rat myosin light chain gene was expressed in skeletal muscle; the mouse 
alpha fetoprotein gene was expressed in yolk sac and liver; the mouse kappa light 
chain (Ig) gene was expressed in B cells; and the mouse mu heavy chain (Ig) 
was expressed in B and T cells. Levels of expression of these proteins vary in 
transgenic animals. For example, rat elastase 1 was expressed at a level 
1200 percent above endogenous expression; however, only two percent more mouse/ 
human beta-globin was expressed. Gene expression levels vary frcm mouse to 
mouse and frcm gene to gene. The level of expression does not usually correlate 
with gene copy number. 
Dr. Scangos said tumors arising in trangenic animals microinjected with oncogenes 
ligated to tissue specific regulatory seguences termed "enhancers" appear to 
be tissue type specific. He then described some of the types of tumors which 
arise in transgenic individuals. Choroid plexus papillomas develop within six 
months of birth in mice microinjected with the SV40 virus; pancreatic adenoma 
results frcm microinjection of a hybrid gene composed of SV40 seguences and 
the rat elastase 1 gene; insulincma results frcm microinjection of a hybrid 
gene composed of SV40 seguences and the gene for insulin; hepatocellular carcinoma 
and insulinoma result frcm microinjection of a hybrid gene composed of SV40 
seguences and seguences of the virus MT (SV40-MT) , additional pathology observed 
in the offspring of animals injected with SV40-MT are peripheral neuropathy 
and abnormal myelination; mammary carcinoma are observed in lactating females 
microinjected with the hybrid gene composed of enhancer seguences of mouse 
mammarv tumor virus (mmtv) and the myc gene ( MMTV -myc ) ; adrenal neuroblastoma 
are observed in transgenic individuals expressing JC virus genes, additional 
observed pathologv are central nervous system neuropathy and abnormal myelination. 
TTie enhancer seguences are implicated in directing tumor development in micro- 
injected animals to certain types of tissues; the tumors do not occur in tissues 
which would not normally express the gene. For example, transgenic mice bearing 
the myc gene fused to the enhancer elements of MMTV develop mammary tumors 
[ 574 ] 
