Chapter 18, Problem 3P

Sometimes, genes transferred into the mouse genome by pronuclear injection disrupt a gene at the (random) site of integration, resulting in a mutation. In one such case, investigators identified a recessive mutation that causes limb deformity in transgenic mice.

a.	The mutant phenotype could be due to the insertion of the transgene in a particular chromosomal site, or a chance point mutation that arose somewhere in the mouse genome different from the integration site. How could you distinguish between these two possibilities?
b.	The mutation in this example was in fact caused by the insertion of the transgene. How could you use this transgene insertion as a tag for identifying the mutant gene responsible for the aberrant limb phenotype?
c.	The insertion mutation was mapped to chromosome 2 of mice in a region where a recessive mutation called limb deformity (ld) had been identified previously. Mice carrying this mutation are available from a major mouse research laboratory. How could you tell if the ld mutation was in the same gene as the transgene insertion mutation?