A C1976Y missense mutation in the mouse Ip3r1 gene leads to short-term mydriasis and unfolded protein response in the iris constrictor muscles
| Autor: | Yi Wang, Min-Wei Gong, Shun Yang, Meng-Jun Dai, Zheng-Feng Xue, Hong-Ling Wang, Rui Chen, Ya-You Miao, Xiao-Ge Duan, Li Chen, Bing Chen, Chong-Yang Qi, Wan-E Wei |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Original Ip3r1 Mutation Missense Mutagenesis (molecular biology technique) Iris Biology N-ethyl-N-nitrosourea (ENU) medicine.disease_cause General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Mice 0302 clinical medicine medicine Mydriasis Missense mutation Animals Inositol 1 4 5-Trisphosphate Receptors Iris (anatomy) Allele unfolded protein response (UPR) mouse Mutation General Veterinary General Medicine Molecular biology Phenotype 030104 developmental biology medicine.anatomical_structure Oculomotor Muscles Unfolded protein response Unfolded Protein Response Animal Science and Zoology sense organs medicine.symptom 030217 neurology & neurosurgery |
| Zdroj: | Experimental Animals |
| ISSN: | 1881-7122 1341-1357 |
| Popis: | Ip3r1 encodes an inositol 1,4,5-trisphosphate-responsive calcium channel. Mutations in the IP3R1 gene in humans may cause Gillespie syndrome (GS) typically presents as fixed dilated pupils in affected infants, which was referred to as iris hypoplasia. However, there is no report of mice with Ip3r1 heterozygous mutations showing dilated pupils. Here, we report a new Ip3r1 allele with short-term dilated pupil phenotype derived from an N-ethyl-N-nitrosourea (ENU) mutagenesis screen. This allele carries a G5927A transition mutation in Ip3r1 gene (NM_010585), which is predicted to result in a C1976Y amino acid change in the open reading frame of IP3R1 (NP_034715). We named this novel Ip3r1 allele Ip3r1C1976Y. Histology and pharmacological tests show that the dilated pupil phenotype is a mydriasis caused by the functional defect in the iris constrictor muscles in Ip3r1C1976Y. The dilated pupil phenotype in Ip3r1C1976Y was referred to as mydriasis and excluding iris hypoplasia. IHC analysis revealed increased expression of BIP protein, the master regulator of unfolded protein response (UPR) signaling, in Ip3r1C1976Y mice that did not recover. This study is the first report of an Ip3r1 mutation being associated with the mydriasis phenotype. Ip3r1C1976Y mice represent a self-healing model that may be used to study the therapeutic approach for Ip3r1-related diseases. |
| Databáze: | OpenAIRE |
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