Testicular amplification 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 mechanisms conferring this restraint, we created transgenic mice carrying a human butyrylcholinesterase (BCHE) coding sequence, previously found to be amplified in a father and son. Blot hybridization of tail DNA samples revealed somatic transgene amplifications with variable restriction patterns and intensities, suggesting the occurrence of independent amplification events, 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 amplifications of the BCHE transgene and the endogenous acetylcholinesterase and c-raf genes appeared in both testis and epididymis DNA from > 80% of FIII mice. Drastic, selective reductions in testis BCHEmRNA but not in actin mRNA were detected by the PCR amplification of testis cDNA from the transgenic mice, and apparently resulted in the limited transmission of amplified genes. The testicular amplification of the BCHE transgene may potentially represent a general phenomenon with clinical implications in human infertility.
Beeri
R
R
Department of Biological Chemistry, Hebrew University, Jerusalem, Israel.
Gnatt
A
A
Lapidot-Lifson
Y
Y
Ginzberg
D
D
Shani
M
M
Soreq
H
H
Zakut
H
H
D000818:Animals; D001483:Base Sequence; D002091:Butyrylcholinesterase / Q000235:genetics*; D018076:DNA, Complementary / Q000235:genetics*; D004822:Epididymis / Q000201:enzymology; D005784:Gene Amplification; D006801:Humans; D008098:Litter Size / Q000235:genetics; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D010375:Pedigree; D012333:RNA, Messenger / Q000378:metabolism; D013737:Testis / Q000201:enzymology*
D018076:DNA, Complementary; D012333:RNA, Messenger; D002091:Butyrylcholinesterase