Fgf3-Fgf4-cis: A new mouse line for studying Fgf functions during mouse development

Area of Science:

• Developmental Biology
• Genetics
• Molecular Biology

Background:

• Fibroblast growth factor (FGF) signaling is essential for embryonic development and implicated in various diseases.
• Genetic studies in mice have revealed functional redundancy among FGF ligands.
• Studying redundancy between closely located genes like Fgf3 and Fgf4 is challenging due to infrequent genetic recombination.

Purpose of the Study:

• To develop a novel mouse model enabling the study of functional redundancy between Fgf3 and Fgf4.
• To overcome the limitations of studying closely linked genes in cis.

Main Methods:

• Retargeting of Fgf3 and Fgf4 genes in cis within an F1 embryonic stem cell line.
• Generation of an Fgf3 null allele and a conditional Fgf4 allele (Fgf3(Δ)-Fgf4(flox)-cis).
• Confirmation of cis targeting using allele-specific single-nucleotide polymorphisms.

Main Results:

• Successful generation of the Fgf3(Δ)-Fgf4(flox)-cis mouse line.
• Demonstrated increased severity of caudal axis extension defects when both Fgf4 and Fgf3 are inactivated.
• Validated the utility of the new mouse line for studying gene redundancy.

Conclusions:

• The Fgf3(Δ)-Fgf4(flox)-cis mouse line provides a powerful tool for investigating FGF gene redundancy.
• This model will facilitate research into the roles of Fgf3 and Fgf4 in various developmental processes and disease contexts.