Directed expression of an oncogene to Sertoli cells in transgenic mice using mullerian inhibiting substance regulatory sequences.
Mullerian inhibiting substance (MIS) is a glycoprotein hormone expressed by Sertoli cells that induces the regression of Mullerian ducts during development of the male reproductive tract. Transgenic mice carrying a fusion gene composed of human MIS transcriptional regulatory sequences linked to the SV40 T-antigen gene specifically develop testicular tumors composed of a cell type histologically resembling the Sertoli cell. The lack of pathology at other sites suggests tissue-restricted expression of the transgene. A cell line derived from one of the testicular tumors has been established that continues to express markers associated with Sertoli cells, such as transferrin, sulfated glycoprotein-2, and inhibin-beta B. The cell line does not express detectable levels of inhibin-alpha, MIS, or FSH receptor. However, the cells have retained forskolin responsiveness. As adult Sertoli cells cannot be propagated in vitro, the availability of an immortal cell line displaying features characteristic of normal Sertoli cells should aid in subsequent analyses of the biology of this cell type.
Peschon
J J
JJ
Department of Biochemistry, University of Washington, Seattle 98195.
Behringer
R R
RR
Cate
R L
RL
Harwood
K A
KA
Idzerda
R L
RL
Brinster
R L
RL
Palmiter
R D
RD
D000818:Animals; D054304:Anti-Mullerian Hormone; D000952:Antigens, Polyomavirus Transforming / Q000096:biosynthesis* / Q000235:genetics; D002461:Cell Line, Transformed; D005576:Colforsin / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D005813:Genes, Synthetic; D006023:Glycoproteins; D006131:Growth Inhibitors / Q000235:genetics*; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic / Q000378:metabolism; D009857:Oncogenes; D009928:Organ Specificity; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis* / Q000235:genetics; D012045:Regulatory Sequences, Nucleic Acid; D012708:Sertoli Cells / Q000378:metabolism*; D013539:Simian virus 40 / Q000235:genetics; D013735:Testicular Hormones / Q000235:genetics*; D013736:Testicular Neoplasms / Q000235:genetics* / Q000473:pathology
D000952:Antigens, Polyomavirus Transforming; D006023:Glycoproteins; D006131:Growth Inhibitors; D011993:Recombinant Fusion Proteins; D013735:Testicular Hormones; D005576:Colforsin; D054304:Anti-Mullerian Hormone