title: Enlargement of the Axial Length and Altered Ultrastructural Features of the Sclera in a Mutant Lumican Transgenic Mouse Model.
abstract: Lumican (LUM) is a candidate gene for myopia in the MYP3 locus. In this study, a mutant lumican (L199P) transgenic mouse model was established to investigate the axial length changes and ultrastructural features of the sclera. The mouse model was established by pronuclear microinjection. Transgenic mice and wild-type B6 mice were killed at eight weeks of age. Gene expression levels of LUM and collagen type I (COL1) in the sclera were analyzed by quantitative real-time polymerase chain reaction (qPCR), and the protein levels were assessed by Western blot analysis. Ocular axial lengths were measured on the enucleated whole eye under a dissecting microscope. Ultrastructural features of collagen fibrils in the sclera were examined with transmission electron microscopy (TEM). Lumican and collagen type I were both elevated at the transcriptional and protein levels. The mean axial length of eyes in the transgenic mice was significantly longer than that in the wild-type mice (3,231.0 ± 11.2 μm (transgenic group) vs 3,199.7 ± 11.1 μm (controls), p<0.05 =). Some ultrastructural changes were observed in the sclera of the transgenic mice under TEM, such as evident lamellar disorganizations and abnormal inter-fibril spacing. The average collagen fibril diameter was smaller than that in their wild-type counterparts. These results indicate that the ectopic mutant lumican (L199P) may induce enlargement of axial lengths and abnormal structures and distributions of collagen fibrils in mouse sclera. This transgenic mouse model can be used for the mechanistic study of myopia.
authors.affiliation: Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology & Visual Sciences Key Lab, Beijing, China.
authors.forename: Yanzheng
authors.initials: Y
authors.lastname: Song
authors.affiliation: Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology & Visual Sciences Key Lab, Beijing, China.
authors.forename: Fengju
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology & Visual Sciences Key Lab, Beijing, China.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology & Visual Sciences Key Lab, Beijing, China.
authors.forename: Mingshen
authors.initials: M
authors.lastname: Sun
authors.affiliation: Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology & Visual Sciences Key Lab, Beijing, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Tao
authors.affiliation: Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology & Visual Sciences Key Lab, Beijing, China.
authors.forename: Yanchuang
authors.initials: Y
authors.lastname: Liang
authors.affiliation: Department of Pathophysiology, China Medical University, Shenyang, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Ma
authors.affiliation: Department of Pathophysiology, China Medical University, Shenyang, China.
authors.forename: Yanqiu
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Wang
authors.affiliation: Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
authors.forename: Junfeng
authors.initials: J
authors.lastname: Hao
mesh_terms: D000818:Animals; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D000071234:Lumican / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D012590:Sclera / Q000033:anatomy & histology* / Q000648:ultrastructure*
chemical_list: D024042:Collagen Type I; D000071234:Lumican