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Fgf3‐Fgf4‐cis : A new mouse line for studying Fgf functions during mouse development
Author(s) -
Anderson Matthew J.,
Southon Eileen,
Tessarollo Lino,
Lewandoski Mark
Publication year - 2016
Publication title -
genesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.093
H-Index - 110
eISSN - 1526-968X
pISSN - 1526-954X
DOI - 10.1002/dvg.22913
Subject(s) - fibroblast growth factor , biology , genetics , allele , null allele , mutant , embryonic stem cell , genomic imprinting , gene , microbiology and biotechnology , gene expression , receptor , dna methylation
Summary The fibroblast growth factor (FGF) family consists of 22 ligands in mice and humans. FGF signaling is vital for embryogenesis and, when dysregulated, can cause disease. Loss‐of‐function genetic analysis in the mouse has been crucial for understanding FGF function. Such analysis has revealed that multiple Fgfs sometimes function redundantly. Exploring such redundancy between Fgf3 and Fgf4 is currently impossible because both genes are located on chromosome 7, about 18.5 kb apart, making the frequency of interallelic cross‐over between existing mutant alleles too infrequent to be practicable. Therefore, we retargeted Fgf3 and Fgf4 in cis , generating an Fgf3 null allele and a conditional Fgf4 allele, subject to Cre inactivation. To increase the frequency of cis targeting, we used an F1 embryonic stem cell line that contained 129/SvJae (129) and C57BL/6J (B6) chromosomes and targeting constructs isogenic to the 129 chromosome. We confirmed cis targeting by assaying for B6/129 allele‐specific single‐nucleotide polymorphisms. We demonstrated the utility of the Fgf3 Δ ‐Fgf4 flox ‐ cis mouse line by showing that the caudal axis extension defects found in the Fgf3 mutants worsen when Fgf4 is also inactivated. This Fgf3 Δ ‐Fgf4 flox ‐ cis line will be useful to study redundancy of these genes in a variety of tissues and stages in development. genesis 54:91–98, 2016. Published 2016. This article is a US Government work and is in the public domain in the USA.