Transmission distortion and mosaicism in an unusual transgenic mouse pedigree

We have analyzed the structure, expression, and inheritance of a foreign DNA insert of an unusual transgenic mouse, designated MyK-103. The insert is composed of two copies of pMK (a metallothionein-thymidine kinase fusion gene) oriented as inverted repeats. No methylation of the foreign DNA could be detected. The original transgenic mouse was mosaic; 10% to 20% of both somatic and germ cells contained the plasmid insert. The pMK insert has been stably transmitted by females through five generations; however, expression of thymidine kinase is extremely variable in different members of the pedigree. Although males carrying the pMK insert are fertile, they never transmit the pMK insert. We propose that the foreign DNA has disrupted a gene that must be expressed during haploid stages of spermatogenesis.