Investigating the relationships between microRNA-125b1 and Jacobsen Syndrome
Date Issued
2016
Date
2016
Author(s)
Hsieh, Hsien-Wei
Abstract
MicroRNAs (miRNA) are polygenetically highly conserved small non-coding RNAs which regulate gene expression post-polygenetically. MicroRNA-125b (miR-125b) is generated from miR-125b1 and miR-125b2 and highly expressed in brain and neuron. MiR-125b plays an important role in the organism development and differentiation of the neuron system evidenced by many miR-125b knockout animal models including C. elegans, Drosophila and zebrafish. Jacobsen syndrome (JS) is a rare chromosomal deletion disorder, also called 11q terminal deletion disorder. This disease is mainly caused by partial deletion of the long arm of chromosome 11 including the q23.3 to the end of 11q (11q23.3-qter) which results in multiple genes depletion and causes physiological and behavioral abnormalities such as thrombocytopenia, abnormal platelet function, growth retardation, and brain abnormality. Patients may have cognitive learning problem and autism spectrum disorder. There is no single gene knockout animal model mimicking Jacobsen syndrome until now. Since miR-125b1 gene is located in the deletion region of Jacobsen syndrome, the goal of this study is evaluating whether the Mir125b1 heterozygous knockout mice (Mir125b1+/- mice) can be an animal model of Jacobsen syndrome by analyzing the physical condition and the behavior of Mir125b1+/- mice. The weight of Mir125b1+/- 10 week-old mice were lower than their littermate controls groups. Moreover, by analyzing the weight of major organs, the brain weight of Mir125b1+/- mice were decreased compared with their control groups. These results implied the growth of the brain and weight of Mir125b1+/- mice may be affected. Although the platelet abnormality is commonly found in patients with Jacobsen syndrome, the PLT count of Mir125b1+/- mice did not show any significant difference. In multiple behavior tests, Mir125b1+/- mice showed normal mobility, motor coordinating ability, and social behavior; however, the anxiety and depression tendency of Mir125b1+/- mice were significantly increased. These results suggested that Mir125b1+/- mice might have autism spectrum disorder. On the other hand, the consequences of water maze and the barnes maze test were incompatible. It is still controversial whether Mir125b1+/- mice have the spatial learning and memorial problems. To establish the correlation of the deficit of cerebral cortex and depression in Mir125b1+/- mice, the thickness of cortical cortex in Mir125b1+/- E18.5 embryos and 10 week-old mice were measured and both were significantly thinner than their WT controls. In conclusion, my thesis proofed that Mir125b1+/- mice with reduced weight in body and brain and autism-like spectrum disorder behaviors, indicating Mir125b1+/- mice might be a potential animal model of Jacobsen syndrome.
Subjects
microRNA-125b1
Jacobsen syndrome
animal behavior test
gene knockout mice
autism spectrum disorder
Type
thesis
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