The great majority of point mutations found to be responsible for human disease to date result in aberrant splicing of primary gene transcripts or alteration of the protein coding region of the mRNA. Reporter gene assays allow DNA fragments to be tested for their ability to regulate transcription. To generate transgenic mice by microinjection, female mice are first induced to superovulate and then mated. Once a homozygous mutant strain has been derived, both copies of the target gene will be disrupted in every cell of the mice. One application of targeted gene disruption is the creation of mouse strains carrying mutations responsible for human disease. Homologous recombination in ES cells can be used to produce transgenic mice carrying the Cre gene, and with lox sites inserted at each end of the target gene. Downstream of the mouse gene sequence is another selectable marker gene, encoding the herpes simplex virus thymidine kinase gene.