Establishment and Analysis of A Mouse Model of Syndromic Cleft Lip and Palate Induced by All-trans Retinoic Acid

doi:10.13701/j.cnki.kqyxyj.2024.08.009

Abstract

Abstract: Objective: To establish and analyze a mouse model of syndromic cleft lip and palate in mice. Methods: Pregnant mice on gestation day 10.5 (GD10.5) were gavaged with 90 mg/kg of atRA or corn oil and DMSO solvent. Upon euthanasia of pregnant mice on GD17.5, embryos were collected. Stereomicroscope, paraffin embedding and sectioning, and hematoxylin-eosin (HE) staining were used to observe the development of embryos. Immunofluorescence staining was used to verify the expression of retinoic acid receptor alpha (RARα). Results: The embryos in the atRA group showed cleft palate, limb deformities, abnormal molar development, and non-compaction of ventricular myocardium. Immunofluorescence staining showed the expression of RARα increased in molar and palate of embryos of the atRA group. Conclusion: The mouse cleft palate model induced by atRA presents as syndromic cleft lip and palate, and atRA affects the development of mice by activating of RARα receptor.

Key words: all-trans retinoic acid, syndromic cleft lip and palate, congenital heart defects, molar, ameloblasts

WANG Yumeng, CHI Dandan, ZHANG Beibei, DUAN Xiaohong, HUANG Yongqing. Establishment and Analysis of A Mouse Model of Syndromic Cleft Lip and Palate Induced by All-trans Retinoic Acid[J]. Journal of Oral Science Research, 2024, 40(8): 710-714.

References

[1] Saleem K, Zaib T, Sun W, et al. Assessment of candidate genes and genetic heterogeneity in human non syndromic orofacial clefts specifically non syndromic cleft lip with or without palate [J]. Heliyon, 2019, 5(12):e03019.
[2] Stoll C, Levy JM, Beshara D. Roberts's syndrome and clonidine [J]. J Med Genet, 1979,16(6):486-488.
[3] Sharma D, Kumar C, Bhalerao S, et al. Ectrodactyly, ectodermal dysplasia, cleft lip, and palate (EEC syndrome) with tetralogy of fallot: A very rare combination [J]. Front Pediatr, 2015, 3:51.
[4] Ghyselinck NB, Duester G. Retinoic acid signaling pathways [J]. Development, 2019, 146(13):dev167502.
[5] Wang Y, Chen J, Wang X, et al. Novel investigations in retinoic-acid-induced cleft palate about the gut microbiome of pregnant mice [J]. Front Cell Infect Microbiol, 2022, 12:1042779.
[6] 阮文彦,侯宇转,迟丹丹,等.ARHGAP29调控小鼠腭突间充质细胞增殖能力的研究[J].口腔医学研究,2022,38(3):275-279.
[7] Liu X, Liu H, Wu Y, et al. The role of lncRNA Meg3 in the proliferation of all-trans retinoic acid-treated mouse embryonic palate mesenchymal cells involves the Smad pathway [J]. Reprod Toxicol, 2021, 104:1-7.
[8] Jones DM, Fabian B, Kramer B. The effect of retinoic acid on mouse mandibular molar development in vitro, using alkaline phosphatase as a molecular indicator of differentiation [J]. SADJ, 2008, 63(5):276, 278-280.
[9] Morkmued S, Laugel-Haushalter V, Mathieu E, et al. Retinoic acid excess impairs amelogenesis inducing enamel defects [J]. Front Physiol, 2017, 7:673.
[10] Marlétaz F, Holland LZ, Laudet V, et al. Retinoic acid signaling and the evolution of chordates [J]. Int J Biol Sci, 2006, 2(2):38-47.
[11] 张景尚,万修华.眼面心牙综合征的研究进展[J].国际眼科纵览,2016,40(3):213-216.
[12] Aida N, Ohno T, Azuma T. Progress and current status in hajdu-cheney syndrome with focus on novel genetic research [J]. Int J Mol Sci, 2022, 23(19):11374.
[13] da Silva Dalben G, Richieri-Costa A, de Assis Taveira LA. Tooth abnormalities and soft tissue alterations in patients with G/BBB syndrome [J]. Oral Dis, 2008, 14(8):747-753.
[14] Børglum Jensen S, Jacobsen P, Rotne L, et al. Oral findings in DiGeorge syndrome [J]. Int J Oral Surg, 1983, 12(4):250-254.
[15] Mammadova A, Zhou H, Carels CE, et al. Retinoic acid signalling in the development of the epidermis, the limbs and the secondary palate [J]. Differentiation, 2016, 92(5):326-335.
[16] Cao F, Yang Z, Yin L. A fetal mouse model of ventricular non-compaction using retinoic acid [J]. Pathol Res Pract, 2019, 215(8):152496.