Adult Apaf-1-deficient mice exhibit male infertility

Narimon Honarpour, Chunying Du, James A Richardson, Robert E Hammer, Xiaodong Wang, Joachim Herz

Research output: Contribution to journalArticle

167 Citations (Scopus)

Abstract

Release of cytochrome c from the mitochondria, and subsequent binding to apoptotic protease-activating factor-1 (Apaf-1 is a key trigger of apoptotic events. A complex composed of Apaf-1, dATP, and cytochrome c activates a series of cytoplasmic proteases called caspases, leading to apoptotic cell death. We have disrupted the Apaf-1 gene in the mouse. Like previous reports on this knockout model, we find that most Apaf-1 mutants die perinatally and frequently exhibit exencephaly and cranioschesis. We additionally find that the neural lesions that develop in the knockout are due to an excess of neural progenitor cells that manifests as early as embryonic day 9.5 in development. In contrast to previous reports on the Apaf-1 knockout mice, we find that 5% of the mutants successfully survive to adulthood. In these survivors, the brain develops normally, but in males, there is degeneration of spermatogonia resulting in the virtual absence of sperm. Thus, cytochrome c-mediated apoptosis is not absolutely required for normal neural development, but is essential for spermatogenesis. These findings strongly suggest that alternative apoptotic pathways work in conjunction with and parallel to Apaf-1 and can modify its effect on programmed cell death. (C) 2000 Academic Press.

Original languageEnglish (US)
Pages (from-to)248-258
Number of pages11
JournalDevelopmental Biology
Volume218
Issue number2
DOIs
StatePublished - Feb 15 2000

Fingerprint

Male Infertility
Cytochromes c
Apoptotic Protease-Activating Factor 1
Cell Death
Cytochromes c1
Spermatogonia
Neural Tube Defects
Spermatogenesis
Caspases
Knockout Mice
Spermatozoa
Mitochondria
Peptide Hydrolases
Stem Cells
Apoptosis
Brain
Genes

Keywords

  • Apoptosis
  • Caspase
  • Cell death
  • Cytochrome c
  • Male infertility
  • Mouse
  • Neuron

ASJC Scopus subject areas

  • Developmental Biology

Cite this

Adult Apaf-1-deficient mice exhibit male infertility. / Honarpour, Narimon; Du, Chunying; Richardson, James A; Hammer, Robert E; Wang, Xiaodong; Herz, Joachim.

In: Developmental Biology, Vol. 218, No. 2, 15.02.2000, p. 248-258.

Research output: Contribution to journalArticle

Honarpour, Narimon ; Du, Chunying ; Richardson, James A ; Hammer, Robert E ; Wang, Xiaodong ; Herz, Joachim. / Adult Apaf-1-deficient mice exhibit male infertility. In: Developmental Biology. 2000 ; Vol. 218, No. 2. pp. 248-258.
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