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Overexpression of Gly(56)/Gly(80)/Gly(81)-mutant insulin-like growth factor-binding protein-3 in transgenic mice
Silha, JV; Gui, YT; Mishra, S; Leckstrom, A; Cohen, P; Murphy, LJ
刊名ENDOCRINOLOGY
2005-03-01
DOI10.1210/en.2004-0905
146期:3页:1523-1531
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Endocrinology & Metabolism
研究领域[WOS]Endocrinology & Metabolism
关键词[WOS]IGF-I ; CANCER CELLS ; APOPTOSIS ; RECEPTOR ; FIBROBLASTS
英文摘要

IGF-independent effects of IGF-binding protein-3 (IGFBP-3) have been demonstrated in vitro; however, the physiological significance of these effects in vivo is unclear. We generated two transgenic (Tg) mouse strains that overexpress a human Gly(56)/Gly(80)/Gly(81)-mutant IGFBP-3 cDNA. This mutant has a markedly reduced affinity for the IGFs, but retains the IGF-independent effects. Serum levels of mutant IGFBP-3 were 156 +/- 12 and 400 +/- 24 ng/ml in hemizygous mice of strains 5005 and 5012, respectively. When Tg and wild-type mice were compared, there was no reduction in birth weight, litter size, or postnatal growth. Despite differences in transgene expression in various tissues, relative organ weight was similar in Tg and wild-type mice, with exception of brain, where a modest reduction in brain weight was observed in the high-expressing 5012 lineage. There was also a significant reduction in proliferating cell nuclear antigen-staining cells observed in the periventricular region of the developing brain in embryonic d 18 Tg embryos. In the higher expressing 5012 Tg strain, IGF-I and murine IGFBP-3 levels, marker of GH action were increased. Furthermore, there was a positive correlation between mutant IGFBP-3 levels and IGF-I levels and between mutant IGFBP-3 levels and murine IGFBP-3 (P = 0.002 and P < 0.001, respectively). These data indicate that overexpression of mutant IGFBP-3 is not associated with growth retardation. The higher levels of IGF-I and murine IGFBP-3 in the 5012 Tg strain suggest that the growth inhibitory effect of mutant IGFBP-3 may be compensated for by other mechanisms.

语种英语
WOS记录号WOS:000227035400064
引用统计
被引频次:25[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/54743
专题北京大学深圳医院_生殖医学科
作者单位1.Univ Manitoba, Dept Physiol, Winnipeg, MB R3E 0W3, Canada
2.Univ Manitoba, Dept Internal Med, Winnipeg, MB R3E 0W3, Canada
3.Peking Univ, Shenzhen Hosp, Ctr Reprod Med, Shenzhen 518036, Peoples R China
4.Univ Calif Los Angeles, Mattel Childrens Hosp, Dept Pediat, Div Endocrinol, Los Angeles, CA 90095 USA
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GB/T 7714
Silha, JV,Gui, YT,Mishra, S,et al. Overexpression of Gly(56)/Gly(80)/Gly(81)-mutant insulin-like growth factor-binding protein-3 in transgenic mice[J]. ENDOCRINOLOGY,2005,146(3):1523-1531.
APA Silha, JV,Gui, YT,Mishra, S,Leckstrom, A,Cohen, P,&Murphy, LJ.(2005).Overexpression of Gly(56)/Gly(80)/Gly(81)-mutant insulin-like growth factor-binding protein-3 in transgenic mice.ENDOCRINOLOGY,146(3),1523-1531.
MLA Silha, JV,et al."Overexpression of Gly(56)/Gly(80)/Gly(81)-mutant insulin-like growth factor-binding protein-3 in transgenic mice".ENDOCRINOLOGY 146.3(2005):1523-1531.
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