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Ikegawa, M, Han, H, Okamoto, A, Matsui, R, Tanaka, M, Omi, N, Miyamae, M, Toguchida, J and Tashiro, K (2008) Syndactyly and preaxial synpolydactyly in the single Sfrp2 deleted mutant mice. Dev. Dyn. 237:2506-17
Secreted Frizzled-related protein 2 (Sfrp2) or Stromal Cell Derived Factor-5 (SDF-5) is highly expressed in the developing limbs. Here we showed the single Sfrp2 inactivation in mice resulted in syndactyly and preaxial synpolydactyly, predominantly in the hindlimbs. Tails were often kinked. A penetrance of the syndactyly was highest in 129/SvJ or CBA/N x 129/SvJ background and the phenotype was haploinsufficient. Preaxial synpolydactyly was seen in homozygous mutants in C57BL/6 x 129/SvJ. Of note, syndactyly showed retarded apoptosis of the second and the third interdigital spaces; concomitantly, mesodermal Msx2 expression was down-regulated. Impaired digital anlagen maturation was also noticeable in the same position. Preaxial synpolydactyly of the Sfrp2 mutants was a non-mirror image type and Shh independent. Although joint formation was not disrupted, chondrocyte maturation was preaxially disturbed. Our results suggest that the Sfrp2 deleted mice can be a useful animal model to study human syndactyly/preaxial synpolydactyly defects.
Animals; Apoptosis/genetics; Apoptosis/physiology; Chondrogenesis/genetics; Chondrogenesis/physiology; Gene Expression Regulation, Developmental; In Situ Hybridization; Limb Deformities, Congenital/genetics; Limb Deformities, Congenital/pathology; Membrane Proteins/genetics; Membrane Proteins/physiology; Mice; Mice, Mutant Strains; Polydactyly/genetics; Polydactyly/pathology; Syndactyly/genetics; Syndactyly/pathology