P0-Cre transgenic mice for inactivation of adhesion molecules in Schwann cells

P0-Cre transgenic mice for inactivation of adhesion molecules in Schwann cells
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DOI:
10.1111/j.1749-6632.1999.tb08574.x
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发表时间:
1999-01-01
期刊:
CHARCOT-MARIE-TOOTH DISORDERS
影响因子:
--
通讯作者:
Wrabetz, L
Wrabetz, L
中科院分区:
其他
文献类型:
--
作者:
Feltri, ML;D'Antonio, M;Wrabetz, L

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正常的周围神经髓鞘形成依赖于雪旺基底膜相互作用。雪旺细胞基板的一个重要组成部分是层粘连蛋白-主要是层粘连蛋白2和层粘连蛋白4,这两种亚型共同的- 2链突变与小鼠(dy)和人类(先天性肌营养不良)的髓鞘发育异常有关。因此,层粘连蛋白2和4受体也可能对髓磷脂的形成起重要作用。在髓磷脂形成的雪旺细胞的基底层表面检测到几种层粘连蛋白2/4受体,即α 6 β 4和α 6 β 1整合素和不良糖聚糖。将这些受体与髓鞘形成联系起来的证据是提示性的,但不是决定性的,遗传学研究还没有证实这些分子在髓鞘形成中的作用,自然或靶向的- 6,- 4和- 1整合素和糖异常蛋白的失活对其他组织有深远的影响,导致胚胎或围产期死亡,因此,有条件地失活这些受体,特别是在髓鞘形成的雪旺细胞中,我们构建并初步鉴定了一种P-0-Cre转基因,该转基因可激活cre介导的外周神经中含loxp基因的重组。
Normal peripheral nerve myelination depends on Schwann tell-basal Lamina interactions. An important component of Schwann cell basal lamina is laminin-predominantly laminins 2 and 4, Mutations in the alpha 2 chain common to these two isoforms are associated with dysmyelination in mouse (dy) and man (congenital muscular dystrophy). Thus, laminin 2 and 4 receptors are also Likely to be important for myelin formation, Several laminin 2/4 receptors are detected at the basal lamina surface of myelin-forming Schwann cells, namely, alpha 6 beta 4 and alpha 6 beta 1 integrins and dystroglycan. The evidence linking these receptors to myelination is suggestive, but not conclusive, Genetic studies have not Jet confirmed a role for these molecules in myelin formation, Natural or targeted inactivation of alpha 6, beta 4, and beta 1 integrins and of dystroglycan hare profound effects on other tissues causing embryonic or perinatal death before myelination, Therefore, to conditionally inactivate these receptors specifically in myelin-forming Schwann cells, we have constructed and initially characterized a P-0-Cre transgene that activates Cre-mediated recombination of loxP-containing genes in peripheral nerve.