Renal failure causes early death of bcl-2 deficient mice
Renal failure causes early death of bcl-2 deficient mice
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DOI：
10.1016/j.mad.2006.02.009
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发表时间：
2006-07-01
影响因子：
5.3
通讯作者：
Kneitzf, Burkhard
中科院分区：
文献类型：
--
作者：
Fedorov, Lev M.;Schmittwolf, Carolin;Kneitzf, Burkhard
BCL-2作为死亡抑制分子在进化保守的细胞死亡途径中起作用。bcl-2在小鼠中的失活可导致多种影响，包括出生后生长迟缓、淋巴组织大量凋亡、多囊肾病（PKD）和寿命缩短。为了评估受损的bcl-2缺陷肾脏对bcl-2敲除小鼠出生后发育和寿命的影响，我们采用了“拯救（n - 1）受损组织”策略。根据该策略，bcl-2杂合动物与H2K-hbcl-2转基因小鼠杂交，在除肾脏外的大多数组织和器官中表达人bcl-2。在bcl-2（-/-）小鼠中，过表达hBCL-2可缓解生长迟缓，使造血淋巴系统恢复正常，并保护其免受γ辐射的影响。然而，hbcl-2转基因在肾脏中不表达，获救的小鼠有PKD，寿命缩短。因此，我们的结果表明PKD是bcl-2缺陷小鼠早期死亡的主要原因。此外，我们还建立了类似肾特异性敲除bcl-2的小鼠模型。这种模型可用于研究单个器官（或组织）中bcl-2或其他基因缺陷对整个生物体发育和衰老的影响。2006爱思唯尔爱尔兰有限公司版权所有。
BCL-2 functions as a death repressor molecule in an evolutionary conserved cell death pathway. Inactivation of bcl-2 in mice results in pleiotropic effects including postnatal growth retardation, massive apoptosis in lymphoid tissues, polycystic kidney disease (PKD) and shortened lifespan. To evaluate the influence of the affected bcl-2 deficient kidneys on the postnatal development and lifespan of bcl-2 knockout mice we used "the rescue of (n - 1) affected tissues" strategy. According to this strategy bcl-2 heterozygous animals were crossed with H2K-hbcl-2 transgenic mice expressing human BCL-2 in most tissues and organs excluding the kidney. Overexpression of hBCL-2 in bcl-2(-/-) mice rescues growth retardation, normalizes and protects the hematolymphoid system from gamma-radiation. However, the hbcl-2 transgene is not expressed in kidneys and the rescued mice have PKD and a shortened lifespan. Thus, our results indicated that PKD is the main reason of early mortality in bcl-2 deficient mice. Moreover, we have created mouse model, similar to the kidney specific knockout of bcl-2. Such models can be useful to study the influence of bcl-2 or other gene deficiency in individual organs (or tissues) on development and ageing of whole organism. (c) 2006 Elsevier Ireland Ltd. All rights reserved.