Fragile X Syndrome (FXS) In Vitro Disease Models

Fragile X syndrome (FXS) is a cognitive disorder caused by silencing of the fragile X mental retardation 1 gene (FMR1) in both males and females with a full mutation. The subsequent lack of FMR1 protein FMRP leads to the dysregulation of hundreds of proteins that affect synaptic plasticity and connectivity in the developing brain leading to intellectual disability (ID) and other clinical features of the syndrome. FXS is one of the most common hereditary mental retardation disorders, accounting for 40% percent of patients with X-linked mental retardation, and currently, there is no effective treatment against FXS, so drugs are limited to control associated symptoms. It is known to lie in the ability of the FMRP to bind to RNA and proteins. However, the exact biological mechanism responsible for the presentation of FXS is not known. This has led many researchers involved in neurological diseases to carry out various research projects on FXS.

Creative Biolabs provides our clients around the world with multiple in vitro disease models to support your research on the pathogenesis of FXS, the development of new drugs, and the screening of new targets.

Necessity of the in Vitro FXS Disease Models

• Epigenetic mechanisms.

The epigenetic silencing of the FMR1 gene that causes FXS occurs only in humans. Epigenetic mechanisms in humans and mice are different and preclude the ability to study epigenetic mechanisms of FMR1 silencing in mouse models of FXS.

• Formation of the brain.

The formation of the brain is prolonged in humans, taking months compared to weeks in mice. More importantly, the human brain is more reliant on the role of interneurons and astrocytes and so FXS mouse models may not adequately reveal differences in these particular systems.

In Vitro FXS Disease Models from Creative Biolabs

• Transgenic cell lines

Creative Biolabs is skilled in the preparation of transgenic cell lines. To prepare FXS cell models, our technicians have successfully established the FMR1 knockout peripheral blood mononuclear cell (PBMC) line, peripheral blood lymphocytes (PBL) line, rat adrenal pheochromocytoma cell (PC12) line, and human chronic myelogenous leukemia cell (K-562) line. If you need in vitro FXS disease models for other cell types, please contact us directly.

• Human pluripotent stem cell (PSCs) models

Human pluripotent stem cells (hPSCs), particularly induced PSCs (hiPSCs), have been used in Creative Biolabs to establish multiple model systems to reveal cellular and molecular events underlying normal and abnormal development in neurological disease. Patient-derived hiPSCs from Creative Biolabs provide a paradigm to understand FXS disease pathogenesis, in the human genetic background.

Fig.1 Establishment and applications of FXS disease model derived from hiPSC.

FMRP plays a crucial role in neuronal development, function, and synaptic plasticity. FMRP deficiency increased the death of immature neurons, leading to reduced neuronal production. Creative Biolabs provides our clients with multiple in vitro models to support your study of the causes and consequences of FMR1 silencing in neural development and function in the human context, please contact us for more information.