Molecular and phenotypic reassessment of an infrequently used mouse model for spinal muscular atrophy.
Molecular and phenotypic reassessment of an infrequently used mouse model for spinal muscular atrophy.
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DOI：
10.1016/j.bbrc.2009.11.090
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发表时间：
2010-01-01
影响因子：
3.1
通讯作者：
DiDonato, Christine J.
中科院分区：
文献类型：
--
作者：
Gogliotti, Rocky G.;Hammond, Suzan M.;Lutz, Cathleen;DiDonato, Christine J.
近端脊髓性肌萎缩症（SMA）是由于运动神经元1 （SMN1）存活基因的缺失，而其几乎相同的同源基因SMN2保留。SMN2拷贝数与疾病严重程度有直接关系。老鼠没有Smn2基因，因此不能自然地复制这种疾病。然而，使用SMN2-BAC转基因小鼠在突变的Smn背景下繁殖，已经产生了两种小鼠SMA模型。在这些情况下，小鼠在出生后不久死亡，在同一胎中具有可变表型，或完全纠正SMA表型。这两种型号都已进口到杰克逊实验室，分发给研究界。为了确保输入到杰克逊实验室后获得的结果与文献中最初报道的结果相似，我们已经开始对这些小鼠模型进行分子和表型评估。在此，我们报告了台湾Li组沉积的SMA小鼠模型的研究结果。这些小鼠，JAX股票号TJL-005058，是SMN2转基因Tg(SMN2)2Hung的纯合子，以及缺乏外显子7 Smn1tm1Hung的靶向Smn等位基因。我们的发现与最初报道的这条线一致，并澄清了一些原始数据。此外，我们克隆并绘制了Tg(SMN2)2Hung在4号染色体上的整合位点，并提供了一种针对该连接片段的简单基因分型分析。最后，基于遗传杂交的存活数据，我们认为这种未被充分利用的SMA模型可能是一种有用的补充或替代更常用的“delta7”SMA小鼠。我们提供了两种基因型小鼠的繁殖方案，以便50%的产仔将是类似sma的幼鼠，而50%将是对照组。
Proximal spinal muscular atrophy (SMA) results from loss of the survival motor neuron 1 (SMN1) gene, with retention of its nearly identical homolog, SMN2. There is a direct correlation between disease severity and SMN2 copy number. Mice do not have a Smn2 gene, and thus cannot naturally replicate the disorder. However, two murine models of SMA have been generated using SMN2-BAC transgenic mice bred onto a mutant Smn background. In these instances mice die shortly after birth, have variable phenotypes within the same litter, or completely correct the SMA phenotype. Both models have been imported to the Jackson Laboratory for distribution to the research community. To ensure that similar results are obtained after importation to The Jackson Laboratory to what was originally reported in the literature, we have begun a molecular and phenotypic evaluation of these mouse models. Here we report our findings for the SMA mouse model that has been deposited by the Li group from Taiwan. These mice, JAX stock number TJL-005058, are homozygous for the SMN2 transgene, Tg(SMN2)2Hung, and a targeted Smn allele that lacks exon 7, Smn1tm1Hung. Our findings are consistent with those reported originally for this line and clarify some of the original data. In addition, we have cloned and mapped the integration site for Tg(SMN2)2Hung to Chromosome 4, and provide a simple genotyping assay that is specific to the junction fragment. Finally, based upon the survival data from our genetic crosses, we suggest that this underused SMA model may be a useful compliment or alternative to the more commonly used “delta7” SMA mouse. We provide breeding schemes in which two genotypes of mice can be generated so that 50% of the litter will be SMA-like pups while 50% will be controls.
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影响因子：
64.5
作者：
LEFEBVRE, S;BURGLEN, L;MELKI, J
通讯作者：
MELKI, J
影响因子：
5.3
作者：
Grondard, C;Biondi, O;Charbonnier, F
通讯作者：
Charbonnier, F
影响因子：
15.9
作者：
Avila, Amy M.;Burnett, Barrington G.;Sumner, Charlotte J.
通讯作者：
Sumner, Charlotte J.
影响因子：
3.5
作者：
Coovert, DD;Le, TT;Burghes, AHM
通讯作者：
Burghes, AHM
DOI：
10.1073/pnas.94.18.9920
发表时间：
1997-09-02
影响因子：
11.1
作者：
Schrank, B;Gotz, R;Sendtner, M
通讯作者：
Sendtner, M