"Once you had enough of these genes," Capecchi explained, "you had enough complexity in the network to allow development of vertebrates, and eventually we came along." * * * Knocking Out a Hox Gene Researchers are studying how certain genes, called Hox genes, control proper development of embryos. To see what each Hox gene does, researchers replace a normal Hox gene with a non-working copy of the gene in mice and see what defects result during gestation.

1. Stem cells, the earliest cells formed after fertilization, are removed from a mouse embryo when the embryo is only a few hours old and has only a few cells. Each stem cell is {INCHES}totipotent, {INCHES} capable of growing into an entire mouse. 2. DNA designed to replace the Hox gene is injected into the stem cell, knocking out the normal gene's function. 3. The altered stem cells are allowed to multiply briefly in a laboratory dish, then are injected into tiny mouse embryos. 4. The embryos are implanted into surrogate mothers. When born, these are {INCHES}mosaic {INCHES} animals, made partly of normal cells and partly of engineered cells. They appear normal because they carry one good copy of the gene, which overrides the damage. But some make sperm or eggs that contain only the altered gene. 5. The mosaic mice are crossbred to produce baby mice with no {INCHES}good {INCHES} copy of the Hox gene. They die at birth, and study shows which tissues are missing because of Hox gene damage.

1) Color Photo by Terry Newfarmer- Mario R. Capecchi, a leading molecular geneticist. 1) Newsday Cover Illustration by Bob Newman- Genetic diagram of a rat. 2) Newsday Color Illustration by Bob Newman- A rat. 3) Newsday color Illustration / CHART by Joe Calviello- Knocking Out a Hox Gene. Researchers are studying how certain genes, called Hox genes, control proper development of embryos. To see what each Hox gene does, researchers replace a normal Hox gene with a non-working copy of the gene in mice and see what defects result during gestation. SOURCE: Howard Hughes Medical Institute; University of Utah. (See end of text).