Association of multiple developmental defects and embryonic lethality with loss of microsomal NADPH-cytochrome P450

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A Novel Strategy Combining Array-CGH, Whole-exome Sequencing and In Utero Electroporation in Rodents to Identify Causative Genes for Brain Malformations
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Published on: December 1, 2017

Anna L Shen1, Kathleen A O'Leary, Charles B Kasper

  • 1McArdle Laboratory for Cancer Research, University of Wisconsin, Madison, Wisconsin 53706-1599, USA.

The Journal of Biological Chemistry
|December 14, 2001
PubMed

Insights

NADPH-cytochrome P450 oxidoreductase (CYPOR) is crucial for embryonic development beyond mid-gestation. Its absence causes severe defects and lethality, highlighting its essential role in later embryonic stages.

Area of Science:

  • Biochemistry
  • Developmental Biology
  • Genetics

Background:

  • Microsomal NADPH-cytochrome P450 oxidoreductase (CYPOR) is the primary electron donor for cytochrome P450 systems.
  • Embryonic development relies on regulated synthesis and degradation pathways involving CYPOR.
  • Early CYPOR expression suggests its importance in early embryogenesis.

Purpose of the Study:

  • To investigate the essential role of CYPOR in mammalian embryonic development.
  • To determine the consequences of CYPOR deficiency on embryogenesis and viability.

Main Methods:

  • Targeted deletion of the CYPOR translation start site and membrane-binding domain.
  • Generation of CYPOR knockout (CYPOR -/-) and heterozygous mice.
  • Phenotypic analysis of embryos at various gestational stages.

Main Results:

  • Loss of microsomal CYPOR led to a truncated cytoplasmic protein but did not affect early embryogenesis.
  • CYPOR -/- embryos exhibited defects by day 10.5, with lethality by day 13.5.
  • Defects included cell adhesion issues, abnormal development (Type I and II), and reduced heterozygote viability.

Conclusions:

  • Microsomal CYPOR is essential for embryonic development past mid-gestation.
  • CYPOR deficiency results in severe embryonic abnormalities and mid-gestational lethality.
  • Loss of one CYPOR allele also contributes to embryonic lethality.

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