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Publication : In vivo actions of insulin-like growth factor-I (IGF-I) on cerebellum development in transgenic mice: evidence that IGF-I increases proliferation of granule cell progenitors.

First Author  Ye P Year  1996
Journal  Brain Res Dev Brain Res Volume  95
Issue  1 Pages  44-54
PubMed ID  8873975 Mgi Jnum  J:34873
Mgi Id  MGI:82328 Doi  10.1016/0165-3806(96)00492-0
Citation  Ye P, et al. (1996) In vivo actions of insulin-like growth factor-I (IGF-I) on cerebellum development in transgenic mice: evidence that IGF-I increases proliferation of granule cell progenitors. Brain Res Dev Brain Res 95(1):44-54
abstractText  The in vivo actions of insulin-like growth factor-I (IGF-I) on cerebellum development have been investigated in transgenic (Tg) mice (IGF-II/I Tg mice) in whom an IGF-II promoter-driven IGF-I transgene is highly expressed in cerebellum. Compared to normal littermates, the brains of IGF-II/I Tg mice exhibited overgrowth beginning from the second week of postnatal life. Among the brain regions examined, cerebellum exhibited the greatest increase in size, such that by 50 days of age cerebellar weight and DNA content were increased by 90% and 143%, respectively, compared to littermate controls. Morphological studies of adult IGF-II/I Tg mice showed that the total number of granule and Purkinje cells was increased by 82% and 20%, respectively, findings consistent with the increased cerebellar DNA content and indicating that the increased cerebellar weight was due in part to an increase in cell number. The thickness of the molecular layer also was increased in IGF-II/I Tg mice. During early postnatal development the number of external granular layer cells, as well as the number of BrdU labeled external granular cells, was increased. These data strongly indicate that IGF-I increases granule cell number by a mechanism that involves the stimulation of granule cell progenitor proliferation. Our findings also indicate that IGF-I influences the growth of Purkinje cells and possibly of other cell types in the cerebellum.
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