Plzf is required in adult male germ cells for stem cell self-renewal

Nat Genet. 2004 Jun;36(6):647-52. doi: 10.1038/ng1366. Epub 2004 May 23.


Adult germline stem cells are capable of self-renewal, tissue regeneration and production of large numbers of differentiated progeny. We show here that the classical mouse mutant luxoid affects adult germline stem cell self-renewal. Young homozygous luxoid mutant mice produce limited numbers of normal spermatozoa and then progressively lose their germ line after birth. Transplantation studies showed that germ cells from mutant mice did not colonize recipient testes, suggesting that the defect is intrinsic to the stem cells. We determined that the luxoid mutant contains a nonsense mutation in the gene encoding Plzf, a transcriptional repressor that regulates the epigenetic state of undifferentiated cells, and showed that Plzf is coexpressed with Oct4 in undifferentiated spermatogonia. This is the first gene shown to be required in germ cells for stem cell self-renewal in mammals.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Base Sequence
  • Cell Differentiation
  • Codon, Nonsense
  • DNA / genetics
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • Epigenesis, Genetic
  • Kruppel-Like Transcription Factors
  • Male
  • Mice
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Octamer Transcription Factor-3
  • Promyelocytic Leukemia Zinc Finger Protein
  • Spermatogonia / cytology*
  • Spermatogonia / metabolism
  • Spermatogonia / transplantation
  • Stem Cells / cytology*
  • Stem Cells / metabolism
  • Testis / cytology
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism


  • Codon, Nonsense
  • DNA-Binding Proteins
  • Kruppel-Like Transcription Factors
  • Octamer Transcription Factor-3
  • Pou5f1 protein, mouse
  • Promyelocytic Leukemia Zinc Finger Protein
  • Transcription Factors
  • Zbtb16 protein, mouse
  • DNA