Mouse model for human sepiapterin reductase deficiency = Sepiapterin reductase 결핍에 대한 생쥐 모델

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Tetrahydrobiopterin $(BH_4)$ is an essential cofactor for several enzymes, including all three forms of nitric oxide synthases, phenylalanine-4-hydroxylase, tryptophan-5-hydroxylase, tyrosine-3-hydroxylase, and glyceryl-ether mono-oxygenase. Therefore, a proper level of $BH_4$ is necessary for controlling the level of phenylalanine and the production of nitric oxide, catecholamines, and serotonin. $BH_4$ deficiency has been shown to be closely associated with diverse neurological disorders, including pediatric neurotransmitter disorders, hyperphenylalaninemia, depression, autism, Parkinson’s disease, and dopamine-responsive dystonia (Segawa’s disease), to name a few. Sepiapterin reductase (SR) is an enzyme that catalyzes the final step of $BH_4$ biosynthesis. While the number of cases of neurological disorders resulting from deficiencies of other catalytic enzymes involved in $BH_4$ biosynthesis and metabolism has been accumulating, only a handful of cases of SR deficiency have been reported, and the role of SR in $BH_4$ biosynthesis in vivo has been poorly understood. Here, I report that the homeostasis of $BH_4$, dopamine, Norepinephrine, serotonin, and phenylalanine are greatly disturbed in $Spr^{-/-}$ mice, which exhibited dwarfism and impaired body movement. Oral supplementation of $BH_4$ and neurotransmitter precursors completely rescued dwarfism and phenylalanine metabolism. The biochemical and behavioral characteristics of $Spr^{-/-}$ mice share striking similarities with the symptoms observed in SR deficiency patients.
Advisors
Chung, Jae-Hoonresearcher정재훈researcher
Description
한국과학기술원 : 생명과학과,
Publisher
한국과학기술원
Issue Date
2006
Identifier
254181/325007  / 020005181
Language
eng
Description

학위논문(박사) - 한국과학기술원 : 생명과학과, 2006.2, [ vii, 116 p. ]

Keywords

Tetrahydrobiopterin; Sepiapterin Reductase; Knockout; 유전자적중; Tetrahydrobiopterin; 세피아테린 환원효소

URI
http://hdl.handle.net/10203/27604
Link
http://library.kaist.ac.kr/search/detail/view.do?bibCtrlNo=254181&flag=dissertation
Appears in Collection
BS-Theses_Ph.D.(박사논문)
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