Double trans-chromosomic mice: maintenance of two individual human chromosome fragments containing Ig heavy and kappa loci and expression of fully human antibodies.
Double trans-chromosomic mice: maintenance of two individual human chromosome fragments containing Ig heavy and kappa loci and expression of fully human antibodies.
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双转染色体小鼠：维持含有Ig重链和κ基因座的两个单独的人类染色体片段并表达全人类抗体。
DOI：
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发表时间：
2000
影响因子：
11.1
通讯作者：
Isao Ishida
中科院分区：
文献类型：
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作者：
K. Tomizuka;T. Shinohara;Hitoshi Yoshida;H. Uejima;A. Ohguma;Sonoko Tanaka;Kaoru Sato;Mitsuo Oshimura;Isao Ishida
使用人类染色体或其片段作为动物转基因的载体，可能会促进对人类大基因组区域的功能研究。我们在这里描述了含有两个单独的人类染色体片段(Hcf)的双跨染色体(TC)小鼠的产生和分析。将两个可传递的HCF，一个含有Ig重链基因(IgH，约1.5Mb)，另一个含有kappa轻链基因(Igkappa，约2Mb)，导入内源性IgH和Igkappa基因失活的小鼠品系。在得到的双TC/双基因敲除小鼠中，相当大比例的体细胞保留了两种HCFs，在没有小鼠重链和Kappa链的情况下，人Ig重链和kappa链的高水平表达表明了对Ig产生缺陷的挽救。此外，四个人类免疫球蛋白伽马亚类的血清表达谱与人类相似。它们在人血清白蛋白免疫后产生抗原特异性的人抗体反应，并从中获得不同亚型的人血清白蛋白特异性人单抗。这些结果代表了使用可传递的HCFs的一代小鼠具有人源化的基因座，这表明TC技术可能允许在小鼠或其他动物中实现超兆基大小的复杂基因座的人源化。这类动物不仅可用于研究人类基因组的体内功能，还可用于获得各种治疗产品。
The use of a human chromosome or its fragment as a vector for animal transgenesis may facilitate functional studies of large human genomic regions. We describe here the generation and analysis of double trans-chromosomic (Tc) mice harboring two individual human chromosome fragments (hCFs). Two transmittable hCFs, one containing the Ig heavy chain locus (IgH, approximately 1.5 Mb) and the other the kappa light chain locus (Igkappa, approximately 2 Mb), were introduced into a mouse strain whose endogenous IgH and Igkappa loci were inactivated. In the resultant double-Tc/double-knockout mice, substantial proportion of the somatic cells retained both hCFs, and the rescue in the defect of Ig production was shown by high level expression of human Ig heavy and kappa chains in the absence of mouse heavy and kappa chains. In addition, serum expression profiles of four human Ig gamma subclasses resembled those seen in humans. They mounted an antigen-specific human antibody response upon immunization with human serum albumin, and human serum albumin-specific human monoclonal antibodies with various isotypes were obtained from them. These results represent a generation of mice with "humanized" loci by using the transmittable hCFs, which suggest that the Tc technology may allow for the humanization of over megabase-sized, complex loci in mice or other animals. Such animals may be useful not only for studying in vivo functions of the human genome but also for obtaining various therapeutic products.
小鼠低 lambda 1 链产生的遗传分析。
DOI：
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发表时间：
1986
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Ju,ST;Selsing,E;Huang,MC;Kelly,K;Dorf,ME
通讯作者：
Dorf,ME
使用酵母人工染色体生产转基因小鼠。
DOI：
10.1385/1-59259-065-9:435
发表时间：
2000
期刊：
Methods in molecular biology (Clifton, N.J.)
影响因子：
--
作者：
Jakobovits,A;Lamb,BT;Peterson,KR
通讯作者：
Peterson,KR