Syndactyly and preaxial synpolydactyly in the single Sfrp2 deleted mutant mice.
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.
Ikegawa
Masaya
M
Department of Genomic Medical Sciences, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Han
Hua
H
Okamoto
Akihiko
A
Matsui
Ryosuke
R
Tanaka
Masami
M
Omi
Natsue
N
Miyamae
Mahito
M
Toguchida
Junya
J
Tashiro
Kei
K
D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D020219:Chondrogenesis / Q000235:genetics / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D017403:In Situ Hybridization; D017880:Limb Deformities, Congenital / Q000235:genetics / Q000473:pathology; D008565:Membrane Proteins / Q000235:genetics* / Q000502:physiology; D051379:Mice; D008817:Mice, Mutant Strains; D017689:Polydactyly / Q000235:genetics* / Q000473:pathology; D013576:Syndactyly / Q000235:genetics* / Q000473:pathology; D000094742:Secreted Frizzled-Related Proteins
D008565:Membrane Proteins; C491628:Sfrp2 protein, mouse; D000094742:Secreted Frizzled-Related Proteins