Targeted inactivation of nuclear interaction partner of ALK disrupts meiotic prophase

Development. 2012 Jul;139(14):2523-34. doi: 10.1242/dev.073072. Epub 2012 Jun 13.


NIPA (nuclear interaction partner of ALK) is an F-box-like protein that monitors the timing of mitotic entry. Constitutively active NIPA delays mitotic entry by preventing accumulation of nuclear cyclin B1. Here, we have investigated the consequences of Nipa inactivation by using a conditional knockout strategy. Nipa-deficient animals are viable but show a lower birth rate and reduced body weight. Furthermore, Nipa-deficient males are sterile owing to a block of spermatogenesis during meiotic prophase. Whereas Nipa-/- mouse embryonic fibroblasts show no severe phenotype, Nipa-/- spermatocytes arrest during stage IV of the epithelial cycle with subsequent TUNEL-positive apoptosis resulting from improper synapsis, defects in the repair of DNA double-stranded breaks and synaptonemal complex formation. Moreover, we show nuclear accumulation of cyclin B1 with a subsequent premature increase in G2/M kinase activity in Nipa-/- spermatocytes. Together, these results reveal a novel role for NIPA in meiosis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Cycle / genetics
  • Cell Cycle / physiology*
  • Cyclin B1 / genetics
  • Cyclin B1 / metabolism
  • DNA Breaks, Double-Stranded
  • Flow Cytometry
  • Immunoblotting
  • Immunohistochemistry
  • Immunoprecipitation
  • Male
  • Meiosis / genetics
  • Meiosis / physiology*
  • Mice
  • Mice, Knockout
  • Mice, Mutant Strains
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • RNA, Small Interfering / genetics
  • Spermatocytes / metabolism


  • Ccnb1 protein, mouse
  • Cyclin B1
  • NIPA protein, mouse
  • Nuclear Proteins
  • RNA, Small Interfering