| First Author | Slavkin HC | Year | 1993 |
| Journal | Am J Med Genet | Volume | 47 |
| Issue | 5 | Pages | 689-97; discussion 687-8 |
| PubMed ID | 8266997 | Mgi Jnum | J:14719 |
| Mgi Id | MGI:62882 | Doi | 10.1002/ajmg.1320470521 |
| Citation | Slavkin HC (1993) Rieger syndrome revisited: experimental approaches using pharmacologic and antisense strategies to abrogate EGF and TGF-alpha functions resulting in dysmorphogenesis during embryonic mouse craniofacial morphogenesis. Am J Med Genet 47(5):689-97 |
| abstractText | The major manifestations of Rieger syndrome (RS), an autosomal dominant disorder, include absent maxillary incisor teeth, malformations of the anterior chamber of the eye, and umbilical anomalies [Aarskog et al., 1983: Am J Med Genet 15:29-38; Gorlin et al., 1990: Syndromes of the Head and Neck 3rd ed.]. Linkage of RS to human chromosome 4q markers has been identified with tight linkage to epidermal growth factor (EGF) [Murray et al., 1992: Nat Genet 2:46-48]. Mutations associated with genes of the EGF superfamily are implicated in malformations arising from abnormal development of the first branchial arch [Ardinger et al., 1989: Am J Hum Genet 45:348-353; Sassani et al., 1993: Am J Med Genet 45:565-569]. Down-regulation of EGF during early mouse development results in ablation of tooth formation [Kronmiller et al., 1991: Dev Biol 147:485-488]. Since EGF, TGF-alpha, and EGF receptor (EGFr) transcripts are expressed in the mouse first branchial arch and derivatives, experimental strategies were employed to investigate the consequences of down-regulation of EGF translation and inhibition of EGF receptor during embryonic mandibular morphogenesis. Antisense inhibition of EGF expression produces mandibular dysmorphogenesis with decreased tooth bud size; these effects are reversed by the addition of exogenous EGF to the culture medium [Shum et al., 1993: Development 118:903-917]. Tyrphostin RG 50864, which inhibits EGF receptor kinase activity, inhibits EGF or TGF-alpha stimulation of tyrosine phosphorylation in a concentration-dependent manner and severely retards mandibular development [Shum et al., 1993: Development 118:903-917].(ABSTRACT TRUNCATED AT 250 WORDS) |
