Albinism and Tyrosinase 
duction, only the pigmented mice were found to 
have kidney lesions. Neoplastic changes were lim- 
ited to the kidney and did not occur in the skin. 
These co-injection experiments demonstrate that 
two unrelated genes can become located in close 
proximity to each other in the genome and still 
function in an independent fashion. Moreover, 
this strategy simplifies long-term maintenance 
-of experimental transgenic mice, since the de- 
sired mice can be readily identified by their 
pigmentation. 
An additional question was whether the synthe- 
sis of tyrosinase in some cell type other than mela- 
nocytes or retinal pigment epithelial cells would 
lead to melanin synthesis and pigment formation. 
To answer this question, regulatory sequences 
that were known to be active specifically in lens 
cells were linked to the tyrosinase coding se- 
quences using recombinant DNA techniques, and 
transgenic mice were generated in an albino 
strain of mice. The transgenic mice all devel- 
oped black eyes. Synthesis of tyrosinase in the 
lens led to pigment production in the lens, con- 
firming that the reason lens cells do not nor- 
mally make melanin is because they do not 
normally make the enzyme tyrosinase. Previous 
studies had suggested that pigment synthesis in 
inappropriate cell types might be harmful for 
those cells. In the transgenic mice, the pig- 
mented lens cells show histological evidence of 
cellular injury and inhibition of normal growth. 
When transgenic DNA integrates into the ge- 
nome, it can insert into the middle of an endoge- 
nous gene, causing insertional inactivation of the 
gene. Since our transgenic tyrosinase mice were 
easy to identify and breed, 80 families were 
tested for the presence of insertional mutations. 
Eight families were found that have defects, rang- 
ing from embryonic lethality to male sterility to 
anemia and premature kidney failure. 
One of the mutations is particularly fascinating 
because the homozygous transgenic mice all have' 
an inversion of the left-to-right organization of 
their internal organs. This condition in humans is 
known as situs inversus. Since the factors that 
control polarity in the developing mammalian 
embryo have not yet been identified, we have be- 
gun experiments that will make use of the trans- 
genic insert to try to isolate the regulatory factor 
for situs inversus. The identification and charac- 
terization of such a factor could greatly enhance 
our understanding of embryonic development 
and guide future efforts to help prevent analo- 
gous birth defects in humans. 
308 
