Fgf receptor structure and strategy for deletion of
FgfR2 exon 9 (IIIc). (A) Schematic
structure of FgfR2 highlighting the third Ig loop, a region in which
alternative usage of exons 8 or 9 in FgfR2 leads to the
generation of the IIIb or IIIc isoforms, respectively. TM,
transmembrane domain. (B) The main ligands activating
each of these isoforms. (C) Schematic depiction of mouse
genomic DNA encompassing FgfR2 exons (boxes) 7, 8, 9,
and 10, drawn to scale and showing main restriction enzyme sites
(Av, AvaI; RV,
EcoRV; B, BamHI;
K, KpnI). (D) Targeting
construct showing loxP sequences placed downstream of exon 9, and
flanking the selectable marker gene neo driven by HSV-TK
promoter located upstream of exon 9. Thick lines indicate the extent of
the targeting construct. (E) Homologous recombinant 129
embryonic stem cells were identified by Southern blotting of
BamHI-digested DNA by using a 450-bp genomic probe
located 3′ of target vector sequences (gray bar in D).
Homologous recombinant cells
(FgfR2-IIIc+/neo-flox) yielded a 6.5-kb
fragment and wild type yielded a 5.0-kb fragment. Both 5′ and 3′ joins
were checked by PCR analysis. (F) Hemizygous
(FgfR2-IIIc+/Δ) mutant mice were generated
by crossing FgfR2-IIIcneo-flox/neo-flox with
ZP3-Cre females (34), and then crossing F1 females
carrying one copy of the targeting construct as well as the Cre
transgene with wild-type males. Approximately 50% of such females
gave Cre-mediated excision. (G) Of these excisions, 90%
were complete (FgfR2-IIIc+/Δ);
the remainder excised only the selectable marker
(FgfR2-IIIc+/Δneo-flox),
as determined by PCR using the pair of primers shown in
C. The potential excision product,
FgfR2-IIIc+/neo-Δflox, was not
observed.