TESTICULAR AMPLIFICATION AND IMPAIRED TRANSMISSION OF HUMAN BUTYRYLCHOLINESTERASE CDNA IN TRANSGENIC MICE

Gene amplification occurs frequently in tumour tissues yet is, in gene ral, non-inheritable. To study the molecular mechanisms conferring thi s restraint, we created transgenic mice carrying a human butyrylcholin esterase (BCHE) coding sequence, previously found to be amplified in a father and son. Blot hybridization of tail DNA samples revealed somat ic transgene amplifications with variable restriction patterns and int ensities, suggesting the occurrence of independent amplification event s, in 31% (11/35) of mice from the FII generation but in only 3.5% (2/ 58) of the FIII and FIV generations. In contrast, >10-fold amplificati ons of the BCHE transgene and the endogenous acetylcholinesterase and c-raf genes appeared in both testis and epididymis DNA from >80% of FI II mice. Drastic, selective reductions in testis BCKEmRNA but not in a ctin mRNA were detected by the PCR amplification of testis cDNA from t he transgenic mice, and apparently resulted in the limited transmissio n of amplified genes. The testicular amplification of the BCHE transge ne may potentially represent a general phenomenon with clinical implic ations in human infertility.