When the embryonic stem cells are injected into embryos from mice with a black coat, the chimeric mice that result have a mixture of black and white or light brown hair. When these chimeric mice are mated to mice with a black coat, the offspring receiving a copy of the genes from embryonic stem cells often have tan coats. However, other coat colors are possible for offspring of the original chimeric mouse due to the multiple genes involved in determining mouse coat colors. Since an offspring of a chimeric mouse inherits only one copy of each embryonic stem cell chromosome, additional matings are necessary to produce offspring with two copies of the mutated gene in the absence of the normal gene. The gene responsible for cystic fibrosis was one of the first to be targeted for knock-out to produce a mouse model of a human disease.
Cystic fibrosis is caused primarily by a defective chloride-channel gene.
Beverly Koller at the University of North Carolina School of Medicine successfully targeted a mutation to this gene. The mice produced have defects in chloride secretion and sodium absorption that affect the fluid environment of the lining of the lungs and airways and other epithelial tissues such as those in the digestive and reproductive tracts. These mice have been a major advantage in studying cystic fibrosis. The mice are being used to better understand how mutations in the gene lead to the disease, to test different drug treatments, and to develop gene therapy strategies. When the p53 gene was mutated in mice by Lawrence Donehower and Allan Bradley at the Baylor College of Medicine, these animals developed normally but were prone to spontaneous development of a variety of neoplasms by 6 months of age.