title: Defective eyelid leading edge cell migration in C57BL/6-corneal opacity mice with an "eye open at birth" phenotype.
abstract: Development of the eyelid requires coordination of the cellular processes involved in proliferation, cell size alteration, migration, and cell death. C57BL/6J-corneal opacity (B6-Co) mice are mutant mice generated by the administration of N-ethyl-N-nitrosourea (100 mg/kg). They exhibit the eyelids open at birth phenotype, abnormal round cell shape from tightened F-actin bundles in leading edge keratinocytes at E16.5, and gradual corneal opacity with neovessels. The tip of the leading edge in B6-Co mice did not move forward, and demonstrated a sharp peak shape without obvious directionality. Analysis of the biological characteristics of B6-Co mice demonstrated that abnormal migration of keratinocytes could affect eyelid development, but proliferation and apoptosis in B6-Co mice had no effect. Mutant gene mapping and sequence analysis demonstrated that in B6-Co mice, adenosine was inserted into the untranslated regions, between 3030 and 3031, in the mRNA 3'-terminal of Fgf10. In addition, guanine 7112 was substituted by adenine in the Mtap1B mRNA, and an A2333T mutation was identified in Mtap1B. Quantitative real-time polymerase chain reaction analysis showed that expression of the Hbegf gene was significantly down-regulated in the eyelids of B6- Co mice at E16.5, compared to B6 mice. However, the expression of Rock1, Map3k1, and Jnk1 genes did not show any significant changes. Abnormal keratinocyte migration and down-regulated expression of the Hbegf gene might be associated with impaired eyelid development in B6-Co mice.
authors.affiliation: Laboratory Animals Center, Nantong University, Nantong, China.
authors.forename: L C
authors.initials: LC
authors.lastname: Wu
authors.affiliation: Institute of Comparative Medicine, Nantong University, Nantong, China.
authors.forename: C
authors.initials: C
authors.lastname: Liu
authors.affiliation: Laboratory Animals Center, Nantong University, Nantong, China.
authors.forename: M R
authors.initials: MR
authors.lastname: Jiang
authors.affiliation: Laboratory Animals Center, Nantong University, Nantong, China.
authors.forename: Y M
authors.initials: YM
authors.lastname: Jiang
authors.affiliation: Laboratory Animals Center, Nantong University, Nantong, China.
authors.forename: Q H
authors.initials: QH
authors.lastname: Wang
authors.affiliation: Laboratory Animals Center, Nantong University, Nantong, China.
authors.forename: Z Y
authors.initials: ZY
authors.lastname: Lu
authors.affiliation: Laboratory Animals Center, Nantong University, Nantong, China.
authors.forename: S J
authors.initials: SJ
authors.lastname: Wang
authors.affiliation: Laboratory Animals Center, Nantong University, Nantong, China.
authors.forename: W L
authors.initials: WL
authors.lastname: Yang
authors.affiliation: Laboratory Animals Center, Nantong University, Nantong, China shaoyx@ntu.edu.cn.|Institute of Comparative Medicine, Nantong University, Nantong, China shaoyx@ntu.edu.cn.
authors.forename: Y X
authors.initials: YX
authors.lastname: Shao
mesh_terms: D020413:3' Untranslated Regions; D000199:Actins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002465:Cell Movement; D016764:Cell Polarity; D049109:Cell Proliferation; D048430:Cell Shape; D003315:Cornea / Q000002:abnormalities / Q000254:growth & development / Q000378:metabolism*; D016510:Corneal Neovascularization / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D003318:Corneal Opacity / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004622:Embryo, Mammalian; D005038:Ethylnitrosourea; D005143:Eyelids / Q000002:abnormalities / Q000254:growth & development / Q000378:metabolism*; D051526:Fibroblast Growth Factor 10 / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D066257:Heparin-binding EGF-like Growth Factor / Q000235:genetics* / Q000378:metabolism; D015603:Keratinocytes / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D009153:Mutagens; D010641:Phenotype; D061251:Primary Cell Culture
chemical_list: D020413:3' Untranslated Regions; D000199:Actins; C496464:Fgf10 protein, mouse; D051526:Fibroblast Growth Factor 10; C587884:Hbegf protein, mouse; D066257:Heparin-binding EGF-like Growth Factor; D008869:Microtubule-Associated Proteins; D009153:Mutagens; C085284:microtubule-associated protein 1B; D005038:Ethylnitrosourea