Journal of Otolaryngology and Ophthalmology of Shandong University ›› 2020, Vol. 34 ›› Issue (1): 78-84.doi: 10.6040/j.issn.1673-3770.0.2019.555

Previous Articles     Next Articles

Expression of the alternative splice forms of Col2a1 in mice eyes, ears and cartilage at various development stages

HAO Peixia1, LIU Xiuzheng2, ZHANG Xiaolin1, FAN Yiyan1, DONG Hongliang2, REN Jizhen1, YIN Jingjing1, MA Xiufang1   

  1. 1. Department of Otolaryngology, the Affiliated Binzhou Medical University Hospital, Binzhou 256600, Shandong, China;
    2. Clinical Medicine Laboratory, Binzhou Medical University Hospital, Binzhou 256600, Shandong, China
  • Published:2020-03-06

PDF (PC)

663

Abstract: Objective To study the expression of the alternative splice forms of Col2a1 in mice eyes, ears and cartilage at various development stages and lay a foundation for further understanding the role of Col2a1 in the development and function of these tissues and organs. Methods Obtained eye, ear and cartilage tissues of mice embryos E12.5, E16.5 and postnatal D0, D7, D14, D21, D28, then analyzed the mRNA expression level of the splice forms: IIA, IIB,IIC and IID of Col2a1 through real-time PCR. Results Four splice forms of Col2a1 were detected in three tissues; expression levels of IIA and IIB were higher than IIC and IID, and IIC was the lowest. All splice forms were highiy expressed in eyes and ears at embryonic stages, then decreased at postnatal to adult stages, and splice forms except IIB presented the same trends in cartilage. Expression of IIB was low in the three tissues at the embryonic stage, then its expression increased with development. The ratio of IIA to IIB varied dramatically in cartilage, it was no more than 2 at E12.5, and decreased to 0.004 at D28; while the ratio in eyes and ears also appeared to decline from embryo to adult stages, but was still above 1 at the adult stage. Conclusion Expression of the four splice forms of Col2a1 in eye, ear and cartilage tissue were all regulated by development stages with IIA and IIB being the main forms. IIA expressed actively in all three tissues at embryonic stages, and was replaced by IIB in adult cartilage, while IIA remained higher than IIB in adult eyes and ears.

Key words: Col2a1, Alternative splice form, Development stage, Eye, Ear, Cartilage

CLC Number: 

  • R76
[1] Myllyharju J, Kivirikko KI. Collagens, modifying enzymes and their mutations in humans, flies and worms[J]. Trends Genet, 2004, 20(1):33-43.
[2] Deng H, Huang XJ, Yuan LM. Molecular genetics of the Col2a1-related disorders[J]. Mutat Res Rev Mutat Res, 2016, 768: 1-13. doi:10.1016/j.mrrev. 2016.02.003.
[3] 陈王浩, 陈浩宇. Ⅱ型胶原纤维α1基因(Col2a1)在视网膜脱离中的作用的研究进展[J]. 当代医学, 2013, 19(35): 14-16, 17. doi:10.3969/j.issn.1009-4393. 2013.35.008.
[4] Mc Alinden A, Johnstone B, Kollar J, et al. Expression of two novel alternatively spliced Col2a1 isoforms during chondrocyte differentiation[J]. Matrix Biol, 2008, 27(3): 254-266. doi:10.1016/j.matbio. 2007.10.002.
[5] Spickett C, Hysi P, Hammond CJ, et al. Deep intronic sequence variants in Col2a1 affect the alternative splicing efficiency of exon 2, and may confer a risk for rhegmatogenous retinal detachment[J]. Hum Mutat, 2016, 37(10): 1085-1096. doi:10.1002/humu. 23050.
[6] Richards AJ, Laidlaw M, Whittaker J, et al. High efficiency of mutation detection in type 1 stickler syndrome using a two-stage approach: vitreoretinal assessment coupled with exon sequencing for screening Col2a1[J]. Hum Mutat, 2006, 27(7): 696-704. doi:10.1002/humu. 20347.
[7] McAlinden A, Majava M, Bishop PN, et al. Missense and nonsense mutations in the alternatively-spliced exon 2 of Col2a1 cause the ocular variant of Stickler syndrome[J]. Hum Mutat, 2008, 29(1): 83-90. doi:10.1002/humu. 20603.
[8] Richards AJ, Meredith S, Poulson A, et al. A novel mutation of Col2a1 resulting in dominantly inherited rhegmatogenous retinal detachment[J]. Invest Ophthalmol Vis Sci, 2005, 46(2): 663-668. doi:10.1167/iovs.04-1017.
[9] Go SL, Maugeri A, Mulder JJ, et al. Autosomal dominant rhegmatogenous retinal detachment associated with an Arg453Ter mutation in the Col2a1 gene[J]. Invest Ophthalmol Vis Sci, 2003, 44(9): 4035-4043. doi:10.1167/iovs.02-0736.
[10] McAlinden A, Shim KH, Wirthlin L, et al. Quantification of type II procollagen splice forms using alternative transcript-qPCR(AT-qPCR)[J]. Matrix Biol, 2012, 31(7/8): 412-420. doi:10.1016/j.matbio. 2012.08.002.
[11] Leung AW, Wong SY, Chan D, et al. Loss of procollagen IIA from the anterior mesendoderm disrupts the development of mouse embryonic forebrain[J]. Dev Dyn, 2010, 239(9): 2319-2329. doi:10.1002/dvdy. 22366.
[12] Lewis R, Ravindran S, Wirthlin L, et al. Disruption of the developmentally-regulated Col2a1 pre-mRNA alternative splicing switch in a transgenic knock-in mouse model[J]. Matrix Biol, 2012, 31(3): 214-226. doi:10.1016/j.matbio. 2011.12.004.
[13] Sandell LJ, Morris N, Robbins JR, et al. Alternatively spliced type II procollagen mRNAs define distinct populations of cells during vertebral development: differential expression of the amino-propeptide[J]. J Cell Biol, 1991, 114(6): 1307-1319. doi:10.1083/jcb.114.6.1307.
[14] Sandell LJ, Nalin AM, Reife RA. Alternative splice form of type II procollagen mRNA(IIA)is predominant in skeletal precursors and non-cartilaginous tissues during early mouse development[J]. Dev Dyn, 1994, 199(2): 129-140. doi:10.1002/aja.1001990206.
[15] McAlinden A. Alternative splicing of type II procollagen: IIB or not IIB?[J]. Connect Tissue Res, 2014, 55(3): 165-176. doi:10.3109/03008207. 2014.908860.
[16] McAlinden A, Traeger G, Hansen U, et al. Molecular properties and fibril ultrastructure of types II and XI collagens in cartilage of mice expressing exclusively the α1(IIA)collagen isoform[J]. Matrix Biol, 2014, 34: 105-113. doi:10.1016/j.matbio. 2013.09.006.
[17] Bishop PN, Reardon AJ, McLeod D, et al. Identification of alternatively spliced variants of type II procollagen in vitreous[J]. Biochem Biophys Res Commun, 1994, 203(1): 289-295. doi:10.1006/bbrc. 1994.2180.
[18] Reardor A, Sandell L, Jones CJ, et al. Localizatiom of pN-type IIA procollagen on adult bovine vitreous collagen fibrils[J]. Matrix Biol, 2000, 19(2):169-173.
[19] Hering TM, Wirthlin L, Ravindran S, et al. Changes in type II procollagen isoform expression during chondrogenesis by disruption of an alternative 5' splice site within Col2a1 exon 2[J]. Matrix Biol, 2014, 36:51-63. doi: 10.1016/j.matbio. 2014.04.004.
[1] WANG Min, LIU Hao, JIANG Luhan, TAN Liyue, LI Wen, FU Xiaolong. Packaging of AAV-ie-Tnfaip8l2 and its effect on improving auditory function in Tnfaip8l2-/- mice [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2026, 40(3): 7-15.
[2] ZHANG Guomin, WANG Maohua, GAO Song, WU Wenbin, YU Youjun. Analysis of the surgical efficacy of adhesive otitis media under continuous irrigating mode for endoscopic ear surgery [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2026, 40(3): 16-19.
[3] LI Shiyun, XIE Yan, PAN Jiayu, CHEN Meixin, LONG Dan, ZHANG Chunlin. Meta analysis of clinical efficacy of cochlear implant in elderly patients with postlingual deafness [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2026, 40(3): 20-30.
[4] LI Kai, LUO Dan. Runmu ling formula ameliorates ocular surface damage in dry eye rats by activating the LC3-ATG5 autophagy pathway and inhibiting inflammatory factor expression [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2026, 40(3): 92-101.
[5] WANG Menghui, LI Ao, WEI Hao, JIANG Yue, WU Xingguang, LI Luxi, QIAN Xiaoyun. Multiple mechanisms and clinical warning signs of deafness caused by hepatitis B virus [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2026, 40(3): 110-114.
[6] YANG Guanying, LI Yuanbin. Advances in the application of artificial intelligence to dry eye disease management [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2026, 40(3): 115-120.
[7] WANG Kaijian, WANG Wei, CHEN Xuesheng, FAN Chunsun, HE Yingying, HUANG Dongling, QIAN Cunhui, DING Shujun. Correlation between neutrophil-to-lymphocyte ratio with hearing loss and audiometric thresholds in adults: a cross-sectional study based on NHANES [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2026, 40(2): 18-28.
[8] FANG Lu, LEI Yudan, WANG Hua. Meta-analysis of clinical effect of cyclosporine eye drops in combination with sodium hyaluronate eye drops in the treatment of dry eye syndrome [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2026, 40(2): 65-73.
[9] NING Yuyun, LI Tong, ZHANG Xinxin. Topical pharmacologic treatment of dry eye disease associated with meibomian gland dysfunction [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2026, 40(2): 125-132.
[10] WANG Nuan, WANG Xinyang, JI Changhao, LIU Min, GAO Jiangang, SUN Jin. In vivo proximity labeling of cell-surface proteins in mouse cochlear hair cells [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2026, 40(1): 6-12.
[11] CHENG Zhuo, LIANG Hui, XING Lumin. Research progress and prospect analysis of deep learning technology in the application of pharyngeal and laryngeal endoscopy [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2026, 40(1): 112-119.
[12] LI Yuchen, WANG Xu. The efficacy and safety of scleral lenses in treating severe ocular surface disease [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2026, 40(1): 149-154.
[13] LI Kang, LI Xuanyi, LIU Wen. Diagnosis and treatment of chronic suppurative otitis media combined with fungal infection of the external auditory canal [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2025, 39(6): 23-30.
[14] TAO Duoduo, SHI Bin, ZHAO Yunshu, LI Yonggang, LIU Jisheng. Preliminary study on neurotransmitter levels in the anterior cingulate cortex and their relationship with hearing levels in patients with age-related hearing loss [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2025, 39(6): 31-39.
[15] LI Shuai, HUANG Chunyan, CHANG Mingzhang. Endoscopic correction of caudal septal cartilage deviation:clinical outcome analysis [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2025, 39(6): 65-70.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed   
No Suggested Reading articles found!
Website Copyright: Editorial Office of Journal of Otolaryngology and Ophthalmology of Shandong University
Address: No.27 Shanda South Road, Jinan, Shandong, China. Post code: 250100 Tel: +86-0531-88366912 Email: ebhxb@sdu.edu.cn Supported by Beijing Magtech Co.Ltd