Generation of conditional alleles for Foxc1 and Foxc2 in mice

Amy Sasman1, Carey Nassano-Miller, Kyoo Seok Shim

  • 1Feinberg Cardiovascular Research Institute, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA.

Genesis (New York, N.Y. : 2000)
|April 24, 2012
PubMed

Insights

Conditional mutations in Forkhead box transcription factors (Foxc1 and Foxc2) were generated in mice. This allows researchers to study their specific roles in development and disease without causing early death.

Area of Science:

  • Developmental Biology
  • Genetics
  • Molecular Biology

Background:

  • Forkhead box transcription factors, Foxc1 and Foxc2, are essential for multiple developmental processes, including eye and cardiovascular formation.
  • Previous studies were limited by perinatal lethality in conventional homozygous-null mutations, hindering investigation of cell-type specific and postdevelopmental functions.

Purpose of the Study:

  • To develop conditional-null mouse models for Foxc1 and Foxc2 to overcome the limitations of conventional mutations.
  • To enable detailed characterization of the cell-type specific and postdevelopmental roles of Foxc1 and Foxc2.

Main Methods:

  • Generation of mice with conditional-null Foxc1(flox) and Foxc2(flox) alleles.
  • Induction of gene deletion using Cre-mediated recombination.
  • Analysis of developmental defects in embryos lacking Foxc1 or Foxc2 expression.

Main Results:

  • Conditional alleles retained wild-type function in non-recombined mice, which were viable and fertile.
  • Cre-mediated recombination resulted in embryos lacking Foxc1 or Foxc2 expression (Foxc1(Δ/Δ) or Foxc2(Δ/Δ)).
  • These embryos exhibited developmental defects identical to those seen in conventional homozygous mutants.

Conclusions:

  • The developed conditional mutations provide a powerful tool for studying Foxc1 and Foxc2 functions.
  • These models will facilitate research into the cell-type specific roles of Foxc1 and Foxc2 during development, in disease states, and in adult physiology.