Question

1. Researchers have identified a gene in humans that (when mutant) causes severe dwarfism and mental retardation. This disorder is inherited in an autosomal recessive manner, and the mutant allele is known to be a loss-of-function mutation. The same gene has been found on mice, although a mutant version of the gene has not been discovered in mice. To develop drugs and an effective therapy to treat this disorder, it would be extremely useful to have a mouse model of the disorder. In other words, it would be desirable to develop a strain of mice homozygous for a loss-of-function mutation in the mouse gene. Experimentally, how would you develop such a strain? List all of the steps necessary to accomplish this

Answer 1

One approach would be to use CRISPR-Cas technology. We could begin with mouse oocytes and use CRISPR-Cas technology to introduce a mutation into the gene through the nonhomologous end joining that would cause a small deletion within the gene. Then, the oocytes would be fertilized and introduced into a female mouse that would be responsible to give birth baby mice, which (hopefully) would carry one copy of the mutant gene. (The sperm that fertilized the oocytes can carry a nonmutant copy of the gene). Then, these heterozgyotes would be crossed to each other and ¼ of their offspring would be homozygous for the mutant gene. Most probably, these homozygous mice would be dwarf and exhibit signs of mental impairment. Therefore, the researcher would have a mouse model to study the disease.