The development of diabetes in E2f1/E2f2 mutant mice reveals important roles for bone marrow-derived cells in preventing islet cell loss

被引:71
作者
Li, FX
Zhu, JW
Tessem, JS
Beilke, J
Varella-Garcia, M
Jensen, J
Hogan, CJ
DeGregori, J
机构
[1] Univ Colorado, Hlth Sci Ctr, Dept Mol Genet & Biochem, Denver, CO 80262 USA
[2] Univ Colorado, Hlth Sci Ctr, Dept Med Med Oncol, Denver, CO 80262 USA
[3] Univ Colorado, Hlth Sci Ctr, Dept Pediat, Denver, CO 80262 USA
[4] Univ Colorado, Hlth Sci Ctr, Integrated Dept Immunol, Denver, CO 80262 USA
[5] Univ Colorado, Hlth Sci Ctr, Program Mol Biol, Denver, CO 80262 USA
[6] Univ Colorado, Hlth Sci Ctr, Barbara Davis Ctr Childhood Diabet, Denver, CO 80262 USA
关键词
D O I
10.1073/pnas.2231861100
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Our studies of mice deficient for the E2F1 and E2F2 transcription factors have revealed essential roles for these proteins in the cell cycle control of pancreatic exocrine cells and the regulation of pancreatic beta cell maintenance. Pancreatic exocrine cells in E2f1/E2f2 mutant mice become increasingly polyploid with age, coinciding with severe exocrine atrophy. Furthermore, mice deficient for both E2F1 and E2F2 develop nonautoimmune, insulin-dependent diabetes with high penetrance. Surprisingly, transplantation of wild-type bone marrow can prevent or rescue diabetes in E2f1(-/-)E2f2(-/-) mice. We hypothesize that exocrine degeneration results in a destructive environment for beta cells, which can be alleviated by restoration of the hematopoietic system that is also defective in E2f1(-/-)E2f2(-/-) mice. The demonstration that beta cell maintenance under conditions of stress is influenced by bone marrow-derived cells may provide important insight into the design of therapies to boost islet mass and function in diabetic patients.
引用
收藏
页码:12935 / 12940
页数:6
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