2006 Fiscal Year Final Research Report Summary
Clarification of the genetic mechanisms underlying the regulation for the expression of SHOX, a causative gene for short stature and sdyschomndrosteosis
| Project/Area Number |
17591132
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pediatrics
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| Research Institution | National Research Institute for Child Health and Development |
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Principal Investigator |
OGATA Tsutomu National Research Institute for Child Health and Development, Director, 部長 (40169173)
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| Co-Investigator(Kenkyū-buntansha) |
FUKAMI Maki National Research Institute for Child Health and Development, Chief, 室長 (40265872)
KAGAMI Masayo National Research Institute for Child Health and Development, Research Fellow, 研究員 (70399484)
WADA Yuka National Research Institute for Child Health and Development, Research Fellow, 研究員 (80399485)
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| Project Period (FY) |
2005 – 2006
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| Keywords | SHOX / Regulatory seqiuence / Sex chromosomes / Haploinsufficiency / In silico analysis / Full length cDNA / Enhancer / 3' region |
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| Research Abstract |
The main results obtained in the research period is three-folds.
<Identification of the enhancer region for the SHOX expression>
We have previously studied more than 40 patient with Leri-Weill syndrome, and identified SHOX deletion or mutation in 33 patients. In this research period, we found microdeletions at the 3' region of the SHOX gene in flour patients with no demonstrable SHOX mutation. The smallest overlapping deleted region was determined as 39 kb, and in silica analysis disclosed 6 evolutionally conserved sequences within the 39 kb critical region. Thus, we performed luciferase assay with the evolutionally conserved sequences, and identified that a roughly 800 bp sequence has the transactivation function for the SHOX expression. The results suggest for the first time that the enhancer sequence for SHOX is present in the 800 by region, and support the presence of an enhancer disorder Furthermore, the identification of the molecule regulating the enhancer will permit to clarify the molecular network underlying the SHOX deficiency disorders.
<Production of SHOX cDNA>
We produced the full length SHOX cDNA by synthesizing all the sequence. This was because SHOX was not expressed in skeletal tissues available.
<Production of SHOX transgenic mouse>
To evaluate the effects of SHOX on growth, we made SHOX transgenic mouse. Since SHOX is absent in the mouse, this model mouse can be utilized to analyze the effect of gonadal estrogens and GnRH-analog therapy in SHOX overdosage status. Thus, this is the first step for the gene therapy for growth failure.
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