Effects of all-trans-retinoic acid on limb development in the genetic polydactyly mouse.

Pdn/+ female mice, mated with Pdn/+ males, were treated with 40 mg/kg body weight of all-trans-retinoic acid (RA) intraperitoneally on day 10 or 11 of gestation, and effects on the limb development were investigated. RA treatment induced the shortening of stylopodium and zygopodium. In the present experiment, we focused on the differences between genotypes in the shortening of stylopodium and zygopodium induced by RA. The effects of RA were milder in Pdn/Pdn than +/- (Pdn/+ and/or +/+) fetuses. The differences between genotypes in the effects of RA were more significant in the group treated on day 11 than on day 10 of gestation. Cartilage of stylopodium and zygopodium was longer in day-13 Pdn/Pdn embryos exposed to RA on day 11 of gestation than those in similarly treated +/- embryos. Many apoptotic cells were observed in the mesenchyme of the forelimb plates at 12 hr after injection of RA on day 11 of gestation. These results suggest that the Pdn gene might influence the apoptosis induced by RA in the mesenchymal cells of the limb, causing milder effects in the shortening of stylopodium and zygopodium in Pdn/Pdn fetuses.

[1]  D. Supp,et al.  Enhanced expression of limb malformations and axial skeleton alterations in legless mutants by transplacental exposure to retinoic acid. , 1994, Developmental biology.

[2]  S. V. Bynum Morphogenesis of retinoic acid-induced postaxial polydactyly in mice. , 1991, Teratology.

[3]  F. Suzuki,et al.  Developmental brain abnormalities accompanied with the retarded production of S-100 beta protein in genetic polydactyly mice. , 1990, Brain research. Developmental brain research.

[4]  T. Tanimura,et al.  Aberrant differentiation of neuroepithelial cells in developing mouse brains subsequent to retinoic acid exposure in utero. , 1989, The American journal of anatomy.

[5]  K. Sulik,et al.  Retinoic-acid-induced limb-reduction defects: perturbation of zones of programmed cell death as a pathogenetic mechanism. , 1989, Teratology.

[6]  K. Sulik,et al.  Retinoic-acid-induced limb malformations resulting from apical ectodermal ridge cell death. , 1988, Teratology.

[7]  M. Okamoto,et al.  Developmental anomalies induced by all-trans retinoic acid in fetal mice: I. Macroscopic findings. , 1986, Teratology.

[8]  I. Naruse,et al.  Prevention of Genetic Polydactyly in Polydactyly Nagoya (Pdn) Mice in Vitro by Surgical Treatment of Foot Plate during Embryogenesis , 1986 .

[9]  Lammer Ej,et al.  Retinoic Acid Embryopathy , 1985 .

[10]  Y. Kawarada,et al.  The fate of DNA originally existing in the zygote nucleus during achromosomal cleavage of fertilized echinoderm eggs in the presence of aphidicolin: Microscopic studies with anti‐DNA antibody , 1985, Journal of cellular physiology.

[11]  C. P. Dagg,et al.  Spontaneous and retinoic acid-induced postaxial polydactyly in mice. , 1985, Teratology.

[12]  H. Kalter Experimental teratological studies with the mouse CNS mutations cranioschisis and delayed splotch. , 1985, Journal of craniofacial genetics and developmental biology. Supplement.

[13]  D. Trasler,et al.  Gene-teratogen interaction and its morphological basis in retinoic acid-induced mouse spina bifida. , 1984, Teratology.

[14]  FranzW. Rosa,et al.  TERATOGENICITY OF ISOTRETINOIN , 1983, The Lancet.

[15]  M. Rooze,et al.  Hereditary and induced modifications of the normal necrotic patterns in the developing limb buds of the rat and mouse: facts and hypotheses , 1983 .

[16]  I. Naruse,et al.  Morphogenesis of genetic preaxial polydactyly, polydactyly nagoya, pdn, in mice. , 1982 .

[17]  W. Scott,et al.  Delayed appearance of ectodermal cell death as a mechanism of polydactyly induction , 1977 .

[18]  J. Howard,et al.  Cellular basis of congenital limb deformity induced in mice by vitamin A. , 1977 .

[19]  井上 稔 Differential Staining of Cartilage and Bone in Fetal Mouse Skeleton by Alcian Blue and Alizarin Red S , 1976 .

[20]  D. Kochhar Teratogenic activity of retinoic acid. , 2009, Acta pathologica et microbiologica Scandinavica.

[21]  J. Milaire Histochemical observations on the developing foot of normal, oligosyndactylous (os/&) and syndactylous (sm/sm) mouse embryos. , 1967 .