Gene transfer cures mouse defect.

Gene transfer cures mouse defect

A hereditary defect in synthesis of a crucial blood protein in mice, which constitutes a disease similar to beta thalassemia in humans, has been corrected by the transfer of the corresponding human gene into mouse reproductive cells. Kiran Chada and Frank Constantini of Columbia University in New York City report successful transplantation of the human adult beta-globin gene. They report that in many of the recipient mice and their descendants, the gene is active in producing human beta-globin protein only in the appropriate location, red blood cells. The gene was also expressed at the appropriate time in development--in fetal and adult red blood cells but not in embryonic red blood cells. These results indicate that the regulatory instructions for the expression of the betaglobin gene sit near the gene itself, because they are contained within the DNA segment the scientists have snipped out of the human chromosome.

The finding that a "good' gene can compensate for a "bad' one that is still present is encouraging for potential clinical uses of gene transfer, comments Heiner Westphal of NICHD. While gene transplanation into human reproductive cells is only a distant prospect, gene transfers into bone marrow cells are considered imminent. "Now one worry can be set aside,' Westphal says, "that transferred genes will not be expressed in appropriate amounts.'

The timing of a transplanted gene's expression, however, cannot always be predicated from its behavior in the animal contributing the genes. In other experiments, Chada and Constantini transferred a gene that is expressed in different developmental stages in mouse and human. Once transplanted into a mouse, the human gamma-globin gene shifted its activity to the stage appropriate for the mouse gene, behaving as an embryonic rather than as a fetal gene.