Late arrest of spermiogenesis and germ cell apoptosis in mice lacking the TBP-like TLF/TRF2 gene.
Metazoan genomes encode two related proteins, TBP and the TBP-like factor (TLF/TRF2), sharing a highly conserved saddle-like domain. TLF is highly expressed in a finely regulated pattern in the mouse testis during spermatogenesis. The murine TLF gene has been inactivated using homologous recombination. TLF-/- mice are viable, but mutant male mice are sterile due to a late, complete arrest of spermiogenesis. In mutant animals, spermatogonia and spermatocytes develop normally, but round spermatids undergo apoptosis at step 7. Although the expression of the transcriptional activator CREM and many other postmeiotic genes was unaltered in TLF null mice, several spermiogenesis genes transcribed in late round spermatids appeared to be under TLF control. Hence, TLF is not required for embryonic development in the mouse but is essential for spermiogenesis.
Martianov
I
I
Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, Illkirch, C.U. de Strasbourg, France.
Fimia
G M
GM
Dierich
A
A
Parvinen
M
M
Sassone-Corsi
P
P
Davidson
I
I
D000818:Animals; D017209:Apoptosis; D002457:Cell Extracts; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007248:Infertility, Male / Q000235:genetics; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D011995:Recombination, Genetic / Q000235:genetics; D012689:Sequence Homology, Nucleic Acid; D013091:Spermatogenesis / Q000235:genetics / Q000502:physiology; D013094:Spermatozoa / Q000166:cytology* / Q000378:metabolism*; D035182:TATA Box Binding Protein-Like Proteins; D013737:Testis / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D002457:Cell Extracts; D004268:DNA-Binding Proteins; D035182:TATA Box Binding Protein-Like Proteins; C441409:TBPL1 protein, human; D014157:Transcription Factors