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Targeted inactivation of p12, CDK2 associating protein 1, leads to early embryonic lethality

Yong Kim1, Jim McBride, Lauren Kimlin

  • 1Division of Oral Biology and Medicine, Dental Research Institute, School of Dentistry, University of California Los Angeles, Los Angeles, California, United States of America.

Plos One
|February 21, 2009
PubMed

Insights

Targeted disruption of Cdk2ap1 causes embryonic lethality and craniofacial defects in mice. Cdk2ap1 is essential for early embryogenesis, implantation, and craniofacial development.

Area of Science:

  • Developmental Biology
  • Genetics
  • Molecular Biology

Background:

  • Cyclin-dependent kinase 2-associated protein 1 (Cdk2ap1) inhibits CDK2, regulating the G1/S cell cycle transition.
  • Disruption of Cdk2ap1 function impacts cell cycle progression and embryonic development.

Purpose of the Study:

  • To investigate the role of Cdk2ap1 in murine embryonic development and craniofacial morphogenesis.
  • To determine the consequences of Cdk2ap1 gene disruption on embryonic lethality and developmental defects.

Main Methods:

  • Generation of Cdk2ap1 knockout mice using targeted gene disruption.
  • Timed pregnancies and embryonic staging to analyze lethality.
  • Craniofacial morphology analysis (Snout Length vs. Face Width ratio).
  • Transgenic rescue experiments and mESC teratoma formation assays.

Main Results:

  • Targeted disruption of Cdk2ap1 leads to embryonic lethality between E3.5 and E5.5.
  • Surviving homozygous knockout mice exhibit craniofacial defects, including reduced snout length.
  • Transgenic rescue partially restored survival rates and craniofacial morphology.
  • Cdk2ap1-deficient mESCs showed impaired pluripotency and restricted mesoderm lineage specification.

Conclusions:

  • Cdk2ap1 is crucial for early embryonic survival, implantation, and development.
  • Cdk2ap1 plays a significant role in craniofacial morphogenesis.
  • Loss of Cdk2ap1 function affects embryonic stem cell pluripotency and lineage commitment.

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