A Review of the Genetics and Pathogenesis of Syndactyly in Humans and Experimental Animals: A 3-Step Pathway of Pathogenesis

Table 2

Syndactyly in animal models classified according to the steps shown in Figure 1.

Step affected	Animal model of syndactyly
IA: activation of the WNT canonical signaling or the accumulation of beta catenin	Mice with Lrp4 mutations
IB: suppression of the BMP canonical signaling or the suppression of BMPs/SMADs	(i) Murine limb deformity (Ld) model (Fmn1 deletions resulting in Grem1 overexpression)
	(ii) Transgenic chick with Grem1 overexpression
	(iii) Overexpression of the Bmp antagonist Noggin
	(iv) Inactivation of the Bmp receptor gene Bmpr1a
	(v) Mice deficient in Bmp2 and Bmp4
	(vi) Knockout mice lacking Cx43
	(vii) Selective inactivation of Smad 1 and 5.
	(viii) Hammer toe (Hm) mutant mice.
II: overexpression of FGF8	(i) Suppression of Notch signaling
	(ii) Msx1; Msx2 double-mutant mice
	(iii) Rounded foot mouse mutants (Fras1 loss-of-function)
	(iv) Mice lacking Nidogen 1 and 2.
III: suppression of retinoic acid or suppression of apoptosis/extracellular matrix degradation	(i) Suppression of retinoic acid activity
	(ii) Spdh/Spdh mice
	(iii) Bid, Bim, Puma triple knockout mice
	(iv) Mice deficient in ADAMTS
	(v) Knockout of Akirin2 in the limb ectoderm