Severe impairment of spermatogenesis in mice lacking the CREM gene

Nature. 1996 Mar 14;380(6570):162-5. doi: 10.1038/380162a0.


Spermatogenesis is a complex developmental process that occurs in several phases. A large number of genes have been identified that are expressed during spermatogenesis, but the biological significance of many of these is not yet known. We have used gene targeting to selectively eliminate the transcription factor CREM (cyclic AMP- responsive element modulator), which is thought to be important for mammalian spermatogenesis. Male mice deficient for all CREM proteins are sterile, as their developing spermatids fail to differentiate into sperm, and postmeiotic gene expression in the testis declines dramatically. The cessation of sperm development is not accompanied by decreases in the levels of follicle-stimulating hormone or testosterone. Our findings indicate that the CREM gene is essential for spermatogenesis, and mice deficient for this transcription factor could serve as a model system for the study of idiopathic infertility in men.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Androgens / metabolism
  • Animals
  • Cell Line
  • Cyclic AMP Response Element Modulator
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / physiology*
  • Epididymis / pathology
  • Follicle Stimulating Hormone / blood
  • Gene Targeting
  • Infertility / genetics
  • Leucine Zippers / genetics
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Organ Size
  • Proteins / metabolism
  • RNA / metabolism
  • Repressor Proteins*
  • Spermatogenesis / genetics
  • Spermatogenesis / physiology*
  • Testis / metabolism
  • Testis / pathology
  • Testosterone / blood


  • Androgens
  • DNA-Binding Proteins
  • Proteins
  • Repressor Proteins
  • Cyclic AMP Response Element Modulator
  • Testosterone
  • RNA
  • Follicle Stimulating Hormone