Gene and Protein Expression in Subjects With a Nystagmus-Associated AHR Mutation

Frontiers in Genetics

Rajech Sharkia¹  Celeste Weiss²  Abdussalam Azem²  Natalia Borovok²  Michal Reichenstein²  Bernd Wissinger⁴  Muhammad Mahajnah⁵ 

[1] Beit Berl College, Beit Berl, Israel;Faculty of Life Sciences, School of Neurobiology, Biochemistry and Biophysics, Tel Aviv University, Tel Aviv, Israel;Hillel Yaffe Medical Center, Hadera, Israel;Institute for Ophthalmic Research Centre for Ophthalmology, Eberhard Karls University of Tübingen, Tübingen, Germany;The Ruth and Bruce Rappaport Faculty of Medicine, Technion – Israel Institute of Technology, Haifa, Israel;Triangle Research and Development Center, Kafr Qara, Israel;

关键词: aryl hydrocarbon receptor;    human mutation;    infantile nystagmus;    gene expression;    protein expression;    CYP1A1;   

DOI  :  10.3389/fgene.2020.582796

来源: DOAJ

【 摘 要 】

Recently, a consanguineous family was identified in Israel with three children affected by Infantile Nystagmus and Foveal Hypoplasia, following an autosomal recessive mode of inheritance. A homozygous stop mutation c.1861C > T; p.Q621∗ in the aryl hydrocarbon receptor (AHR) gene (AHR; MIM 600253) was identified that co-segregated with the disease in the larger family. AHR is the first gene to be identified causing an autosomal recessive Infantile Nystagmus-related disease in humans. The goal of this study is to delineate the molecular basis of this newly discovered human genetic disorder associated with a rare AHR gene mutation. The gene and protein expression levels of AHR and selected AHR targets from leukocyte cultures of healthy subjects and the patients were analyzed. We observed significant variation between mRNA and protein expression of CYP1A1, CYP1B1, and TiPARP under rest and AHR-induced conditions. The CYP1A1 enzymatic activity in induced leukocytes also differs significantly between the patients and healthy volunteers. Intriguingly, the heterozygous subjects demonstrate CYP1A1 and TiPARP gene and protein expression similar to homozygous patients. In contrast, CYP1B1 inducibility and expression vary between hetero- and homozygous subjects. Similarity and differences in gene and protein expression between heterozygotes and homozygous patients can give us a hint as to which metabolic pathway/s might be involved in the Nystagmus etiology. Thus, we have a unique human model for AHR deficiency that will allow us the opportunity to study the biochemical basis of this rare human mutation, as well as the involvement of AHR in other physiological processes.

【 授权许可】

Unknown