Disease relevance of py

• Here we describe how the loss of a cytoplasmic multi-PDZ scaffolding protein, glutamate receptor interacting protein 1 (GRIP1), leads to the formation of subepidermal hemorrhagic blisters, renal agenesis, syndactyly or polydactyly and permanent fusion of eyelids (cryptophthalmos) [1].
• The clinical hallmarks are occipital meningoencephalocele, cystic kidney dysplasia, fibrotic changes of the liver and polydactyly [2].
• These mice display many of the characteristics of BWS, including placentomegaly and dysplasia, kidney dysplasia, macroglossia, cleft palate, omphalocele, and polydactyly [3].
• Bardet-Biedl syndrome (BBS) is an autosomal recessive, genetically heterogeneous, pleiotropic human disorder characterized by obesity, retinopathy, polydactyly, renal and cardiac malformations, learning disabilities, and hypogenitalism [4].
• McKusick-Kaufman syndrome (MKS) is an autosomal recessive disorder characterized by post-axial polydactyly, congenital heart defects and hydrometrocolpos, a congenital structural abnormality of female genitalia [5].

Psychiatry related information on py

• Bardet-Biedl syndrome (BBS) is a genetically heterogeneous autosomal recessive disorder with the primary clinical features of obesity, pigmented retinopathy, polydactyly, hypogenitalism, mental retardation and renal anomalies [6].

High impact information on py

• Fidget mice also have small eyes, associated with cell-cycle delay and insufficient growth of the retinal neural epithelium, and lower penetrance skeletal abnormalities, including pelvic girdle dysgenesis, skull bone fusions and polydactyly [7].
• The Xt heterozygotes show craniofacial defects and a polydactyly phenotype similar to GCPS [8].
• Disruption of a long-range cis-acting regulator for Shh causes preaxial polydactyly [9].
• The mice do not have polydactyly or vaginal abnormalities [5].
• The ZRS contains point mutations that segregate with polydactyly in four unrelated families with PPD and in the Hx mouse mutant [10].

Chemical compound and disease context of py

• As in human SPD, the spdh phenotype consists of central polydactyly, syndactyly and brachydactyly and is caused by the expansion of a polyalanine encoding repeat in the 5' region of the Hoxd13 gene [11].
• As a consequence of cellular damages by urethane gas inhalation during pregnancy, significantly high incidence of fetal deaths and congenital malformations (cleft palate, polydactyly, tail anomaly etc.) was induced in the offspring [12].
• Polydactyly and tail anomalies were markedly suppressed by the post-treatment with nicotinamide, while cleft palates were less effectively suppressed [13].
• Prevention of polydactyly manifestation in Polydactyly Nagoya (Pdn) mice by administration of cytosine arabinoside during pregnancy [14].

Biological context of py

• Here, we show that the chromosome 7q36 associated preaxial polydactyly, a frequently observed congenital limb malformation, results from point mutations in a Shh regulatory element [10].
• A long-range Shh enhancer regulates expression in the developing limb and fin and is associated with preaxial polydactyly [10].
• The duplication expands the stretch of alanines from 15 to 22; the same type of expansion occurs in human SPD mutations. spdh/spdh homozygotes exhibit severe malformations of all four feet, including polydactyly, syndactyly and brachydactylia [15].
• Polydactyly is accompanied by a reduction of programmed cell death in the developing hind limb [16].
• A less potent transgene gave rise to partially rescued embryos with massive exencephaly, and polydactyly and branched digits in the limbs [17].

Anatomical context of py

• Taken together these observations suggest that naturally occurring polydactyly could involve recruitment of cells from regions adjacent to the limb buds [18].
• Surprisingly, increasing mutant BAC copy number also leads to the de novo appearance of digit I polydactyly in the hind limb and transformations of the vertebrae [16].
• Distribution of polarizing activity and potential for limb formation in mouse and chick embryos and possible relationships to polydactyly [18].
• The mutant displayed preaxial polydactyly in the hindlimbs of heterozygous embryos, and in both hindlimbs and forelimbs of homozygotes [19].
• doubleridge is a transgene-induced mutation characterized by polydactyly and syndactyly of the forelimbs [20].

Associations of py with chemical compounds

• 5-Bromodeoxyuridine (BrdU) is known as a potent teratogen and has been reported to induce polydactyly and other limb malformations in rodents (DiPaolo, Science 145, 501-503, 1964) [21].
• These findings indicated that a subteratogenic dose of Ara-C prevented the genetic expression of polydactyly in almost all Pdn/+ and some cases of Pdn/Pdn mice.(ABSTRACT TRUNCATED AT 250 WORDS)[14]
• Therefore, mitomycin-C teratogenicity in terms of the manifestation of cervical rib, polydactyly and tail anomaly, but not vertebral anomaly, was suggested to be enhanced by methylmercury [22].
• All-trans retinoic acid (RA) administered on day 10 or 11 of gestation, but not on day 9, increased the incidence of polydactyly at each gestational day examined [23].
• Effects of all-trans-retinoic acid on limb development in the genetic polydactyly mouse [24].

Regulatory relationships of py

• Bapx1 homeobox gene gain-of-function mice show preaxial polydactyly and activated Shh signaling in the developing limb [25].

Other interactions of py

• Enforced expression of any of several 5'Hoxd genes causes polydactyly of different distinct digit types with posterior transformations in a Gli3(+) background, whereas, in Gli3 null limbs, polydactylous digits are all similar, short and dysmorphic, even though endogenous 5'Hoxd genes are broadly misexpressed [26].
• Several naturally occurring mouse mutations with the phenotype of preaxial polydactyly exhibit ectopic Shh expression at the anterior limb margin [27].
• The mouse mutant Doublefoot (Dbf) shows preaxial polydactyly of all four limbs [28].
• Evidence that preaxial polydactyly in the Doublefoot mutant is due to ectopic Indian Hedgehog signaling [27].
• The polydactyly of Dkk1(d/d) mice was corrected by reduced expression of Lrp5 or Lrp6 [29].

Analytical, diagnostic and therapeutic context of py

• Neuro-glial neurotrophic interaction in the S-100 beta retarded mutant mouse (Polydactyly Nagoya). III. Transplantation study [30].
• Neuro-glial neurotrophic interaction in the S-100 beta retarded mutant mouse (Polydactyly Nagoya). II. Co-cultures study [31].
• Fetal laser surgery in genetic polydactyly mice [32].
• Specific long bone reductions occurred after treatment on the 11th or 11.5 day and were accompanied by preaxial polydactyly; treatment on the 12th or 12.5 day produced high incidence of ectrodactyly but no long bone reductions [33].
• A hereditary preaxial polydactyly mouse (Pdn) provides an opportunity to study the effects of this malformation on the surrounding morphological structures and, specifically, on the volar pads, i.e., the sites over which the dermatoglyphic patterns develop [34].

References