Molecular Genetics Studies on Hematopoietic Cells 
lates phagocytic cell function generally as well as 
expression of the cytochrome, it was also possi- 
ble to show that this lymphoid is clinically effec- 
tive in chronic granulomatous disease. Studies 
have identified several point mutations in the cy- 
tochrome that interfere with protein function in 
vivo. We are now working to define the elements 
of the gene responsible for cell-restricted (i.e., 
phagocytic cell) gene expression. Through the 
use of transgenic mice, we identified a DNA frag- 
ment suflBcient for targeting reporter or onco- 
genes in phagocytic cells. Coupled to an onco- 
gene, this fragment leads to the development of 
an inherited malignancy of phagocytes in mice. 
Efforts now are focused on the characterization 
of the cellular components that account for lin- 
eage-specific regulation. In the end, through an 
understanding of normal regulation in white 
blood cells, we envision improved capabilities to 
modulate gene expression and differentiation in 
both health and disease. This will facilitate on- 
going strategies to develop new approaches to 
the treatment of genetic disease by gene transfer 
into marrow stem cells (somatic gene therapy) . 
336 
