Testicular amplificaion and impaired transmission of human butyrylcholinesterase cDNA in transgenic mice

Gene amplification occurs frequently in tumour tissues yet is,in general, non-inheritable. To study the molecular mechanismsconferring this restraint, we created transgenic mice carryinga human butyrylcholinesterase (BCHE) coding sequence, previouslyfound to be amplified in a father and son. Blot hybridizationof tail DNA samples revealed somatic transgene amplificationswith variable restriction patterns and intensities, suggestingthe occurrence of independent amplification events, in 31% (11/35)of mice from the FII generation but in only 3.5% (2/58) of theFII and FIV generations. In contrast, >10-fold amplificationsof the BCHE transgene and the endogenous acetylcholinesteraseand c-raf genes appeared in both testis and epididymis DNA from>80% of FIII mice. Drastic, selective reductions in testisBCHEmRNA but not in actin mRNA were detected by the PCR amplificationof testis cDNA from the transgenic mice, and apparently resultedin the limited transmission of amplified genes. The testicularamplification of the BCHE transgene may potentially representa general phenomenon with clinical implications in human infertility.