Mouse trisomy 16 as an animal model of human trisomy 21 (Down syndrome): production of viable trisomy 16 diploid mouse chimeras.
Mouse trisomy 16 as an animal model of human trisomy 21 (Down syndrome): production of viable trisomy 16 diploid mouse chimeras.
复制标题
小鼠 16 三体作为人类 21 三体（唐氏综合症）的动物模型：生产可行的 16 三体二倍体小鼠嵌合体。
DOI：
10.1016/0012-1606(84)90156-8
复制
发表时间：
1984
影响因子：
2.7
通讯作者：
Epstein,CJ
中科院分区：
文献类型：
--
作者：
Cox,DR;Smith,SA;Epstein,LB;Epstein,CJ
我们此前曾提出，16号染色体的小鼠三体将提供人类21三体(唐氏综合征)的动物模型。然而，这个模型的价值在一定程度上是有限的，因为16三体小鼠胚胎不能作为活着出生的动物存活下来。因此，为了制造出具有16号染色体三体细胞的存活小鼠，我们使用聚合技术产生了三体16↔二倍体(ts 16↔2n)嵌合体。共产生嵌合小鼠79只，其中11只为16只↔2n嵌合体。在这些TS16↔2n小鼠中，有7只在出生前作为胎儿进行了分析，4只作为活体动物进行了分析。与非嵌合的ts 16小鼠胚胎不同，ts 16↔2n小鼠出生前不久死于水肿、先天性心脏病以及胸腺和脾发育不良，但除1只外，所有动物都存活并表现正常。活生生的ts 16↔2n嵌合体中最大的一个在尸检时只有12个月大。经毛色、酶标记和/或核型分析鉴定，7只TS16↔2n嵌合体胎儿的TS16细胞占脑、心、肺、肝、肾的50-60%，4只活体出生的TS16↔2n动物的TS16细胞占这些器官的30-40%。在TS16↔2n嵌合体中，TS16细胞平均占胸腺的40%和脾的80%，没有胸腺或脾发育不良的证据。然而，我们观察到与2n↔2n对照相比，活出生的TS 16↔2n嵌合体的血液、脾、胸腺和骨髓中的TS 16细胞明显不足。这些结果表明，尽管除了一个例外，ts 16↔2n嵌合体是有活力的和表型正常的，但每种动物在包括大脑在内的各种组织中都含有相当大比例的三体细胞。此外，我们的结果表明，尽管在TS16↔2n胎儿中观察到的TS16胸腺和脾细胞的异常发育在很大程度上得到了纠正，但TS16红系和淋巴样细胞与年龄较大的活体TS16↔2n嵌合体中的二倍体细胞相比具有严重的增殖劣势。TS16↔2n嵌合小鼠将为研究非整倍体的功能后果提供一个有价值的工具，并可能为深入了解三体21导致人类发育异常的机制提供线索。
We have previously proposed that mice trisomic for chromosome 16 will provide an animal model of human trisomy 21 (Down syndrome). However, the value of this model is limited to some extent because trisomy 16 mouse fetuses do not survive as live-born animals. Therefore, in an effort to produce viable mice with cells trisomic for chromosome 16, we have used an aggregation technique to generate trisomy 16 ↔ diploid (Ts 16 ↔ 2n) chimeras. A total of 79 chimeric mice were produced, 11 of which were Ts 16 ↔ 2n chimeras. Seven of these Ts 16 ↔ 2n mice were analyzed as fetuses, just prior to birth, and 4 were analyzed as live-born animals. Unlike nonchimeric Ts 16 mouse fetuses which die shortly before birth with edema, congenital heart disease, and thymic and splenic hypoplasia, all but 1 of the Ts 16 ↔ 2n animals were viable and phenotypically normal. The oldest of the live-born Ts 16 ↔ 2n chimeras was 12 months old at the time of necropsy. Ts 16 cells, identified by coat color, enzyme marker, and/or karyotype analyses, comprised 50–60% of the brain, heart, lung, liver, and kidney in the 7 Ts 16 ↔ 2n chimeric fetuses and 30–40% of these organs in the 4 live-born Ts 16 ↔ 2n animals. Ts 16 cells comprised an average of 40% of the thymus and 80% of the spleen in the Ts 16 ↔ 2n chimeras analyzed as fetuses, with no evidence of thymic or splenic hypoplasia. However, we observed a marked deficiency to Ts 16 cells in the blood, spleen, thymus, and bone marrow of live-born Ts 16 ↔ 2n chimeras as compared to 2n ↔ 2n controls. These results demonstrate that although the Ts 16 ↔ 2n chimeras were, with one exception, viable and phenotypically normal, each animal contained a significant proportion of trisomic cells in a variety of tissues, including the brain. Furthermore, our results suggest that although the abnormal development of Ts 16 thymus and spleen cells observed in Ts 16 fetuses is largely corrected in Ts 16 ↔ 2n fetuses, Ts 16 erythroid and lymphoid cells have a severe proliferative disadvantage as compared to diploid cells in older live-born Ts 16 ↔ 2n chimeras. Ts 16 ↔ 2n chimeric mice will provide a valuable tool for studying the functional consequences of aneuploidy and may provide insight into the mechanisms by which trisomy 21 leads to developmental abnormalities in man.
登录
查看更多内容
唐氏综合症的死亡率和生命表
DOI：
--
发表时间：
1975
期刊：
Acta Paediatrica Scandinavica
影响因子：
--
作者：
J. Øster;A. Nielsen
通讯作者：
A. Nielsen
21 三体对人成纤维细胞多肽合成模式的影响。
影响因子：
9.8
作者：
J. Weil;C. Epstein
通讯作者：
C. Epstein
超氧化物歧化酶-1 对 21 号染色体非整倍体有核细胞的剂量影响。
影响因子：
9.8
作者：
William W. Feaster;Lillian W. Kwok;'. CHARLESJ.EPSTEIN
通讯作者：
'. CHARLESJ.EPSTEIN
使用体细胞杂交体和单克隆抗 L 抗体将人类肝型 6-磷酸果糖激酶同工酶 (PFKL) 基因分配至 21 号染色体。
DOI：
10.1073/pnas.78.6.3738
发表时间：
1981
影响因子：
11.1
作者：
Vora,S;Francke,U
通讯作者：
Francke,U
与唐氏综合症、21 号染色体和阿尔茨海默病相关的蛋白质变异 *
影响因子：
5.2
作者：
M. L. Keuren;D. Goldman;C. Merril
通讯作者：
C. Merril