Tetanus toxin light chain expression in Sertoli cells of transgenic mice causes alterations of the actin cytoskeleton and disrupts spermatogenesis.
Tetanus toxin is a powerful neurotoxin known to inhibit neurotransmitter release. The tetanus toxin light chain is a metalloprotease that cleaves some members of the synaptobrevin gene family with high specificity. Here, we report the expression of a synthetic gene encoding the tetanus toxin light chain in the seminiferous epithelium of transgenic mice. Spermatogenesis was severely impaired and mature spermatozoa were completely absent. Late spermatids exhibited pleomorphic shapes and acrosomal distortions. The number of Leydig cells was greatly increased. In situ hybridization analysis revealed that the toxin acts on Sertoli cells. Affected cells exhibited an aberrant distribution of actin filaments and many cells contained large vacuoles. Our results demonstrate that tetanus toxin is active in non-neuronal cells and suggest an important function for members of the synaptobrevin gene family during the late stages of spermatogenesis.
Eisel
U
U
Developmental Biology Unit, National Institute of Mental Health, Bethesda, MD 20892.
Reynolds
K
K
Riddick
M
M
Zimmer
A
A
Niemann
H
H
Zimmer
A
A
D000199:Actins / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000648:ultrastructure*; D005260:Female; D015870:Gene Expression; D005813:Genes, Synthetic; D017403:In Situ Hybridization; D046911:Macromolecular Substances; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D010957:Plasmids; D014176:Protein Biosynthesis; D015183:Restriction Mapping; D012708:Sertoli Cells / Q000378:metabolism* / Q000648:ultrastructure; D013091:Spermatogenesis; D013744:Tetanus Toxin / Q000096:biosynthesis* / Q000235:genetics; D014158:Transcription, Genetic
D000199:Actins; D046911:Macromolecular Substances; D013744:Tetanus Toxin