Genes involved in intercellular signal transduction during melanocyte differentiation in the mouse.

小鼠黑素细胞分化过程中参与细胞间信号转导的基因。

基本信息

批准号：
62540480
负责人：
TAKEUCHI Takuji
金额：
$ 1.02万
依托单位：
TOHOKU UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1987
资助国家：
日本
起止时间：
1987 至 1988
项目状态：
已结题

项目摘要

A signal transduction mechanism in the cell membrance, which receive information from the cellular environment and transfers it to the site of cellular function, has been demonstrated in various cell types. At the final step of melanocyte differentiation in mouse hair follicles, the cells produce melanin. The type of melanin they produce is, however, determined by the tissue. environment of hair follicles. In wild-type mice, melanocytes located in hair bulbs synthesize eumelanin at the beginning of hair growth. They subsequently produce pheomelanin and finally produce eumelanin again. Therefore, the hair is characterized by a subterminal band of yellow, with the rest of it displaying black. This characteristic is called the agouti pattern and is known to be determined by the wild-type allele, A__-, at the a__-(agouti) locus, which is considered to function in the dermal cells. By using an organ culture method, we have demonstrated that the product of the a__- locus (A factor) blocks th … More e action of MSH (melanocyte stimulating hormone) at the・MSH receptor site, and modifies the pathway of melanin biosynthesis. An attempt was made in the present study to clone cDNA for the A factor.Mice homozygous for a__- allele were injected with skin homogenate from the mouse, genotype A^y/a__-, which constitutively produces the A factor. Polyclonal as well as monoclonal antibodies were prepared from these mice. Immunohistochemical localization of the antigen revealed that cells scatterd in dermis were positive. Thses cells, presumably mast cells, ate expected to be the site of the gene action of the a__- locus from the results of previous studies. A cDNA library was constructed from poly (A)^+mRNA from the mouse skin with the genotype A^y/a using gtll vector, and screened with the antibodies. Two clones, A^y11 (2.8 kbp)and A^y9(750 bp), were isolated. Results of the in situ hybridization by using the cDNAs as probes demonstrated that the mRNA hybridized with the A^y11 was located in the dermal cells (presumably mast cells) and that the site of the transcription for A^y9 was melanocyte. Therefore, it is likely that the A^y11 is a cDNA for the A factor and that the A^y9 is a cDNA for a product of secondary gene action induced by the A factor. Less

在各种细胞类型中已经证明了细胞旋律中的信号传递机制，该信号传递机制从细胞环境中接收信息并将其转移到细胞功能位置。在小鼠毛囊中黑素细胞分化的最后一步，细胞会产生黑色素。然而，它们产生的黑色素类型是由组织决定的。毛发环境。在野生型小鼠中，位于头发生长开始时，位于发灯泡的黑素细胞合成了eumelanin。随后，他们产生芬聚氨酸，最后再次产生依umelanin。因此，头发的特征是黄色的亚端带，其余的显示为黑色。该特征称为agouti模式，已知由A __-（Agouti）基因座的野生型等位基因（__-）确定，该位点被认为在皮肤细胞中起作用。通过使用器官培养方法，我们证明了A __-基因座（一个因素）的乘积阻止了MSH（黑色素细胞刺激果烯）在MSH受体位点的更多作用，并修改了黑色素生物合成的途径。在本研究中，试图将A cDNA固定在__-等位基因中，并从小鼠中注入了皮肤匀浆，基因型A^Y/A __-，该基因型均匀产生了A。从这些小鼠制备了多克隆和单克隆抗体。抗原的免疫组织化学定位表明，散布在真皮中的细胞是阳性的。从先前的研究结果中，THSES细胞可能是A __-基因座基因作用的位点。使用GTLL载体的基因型A^Y/A从小鼠皮肤中的聚（A）^+mRNA构建一个cDNA文库，并用抗体进行筛选。隔离了两个克隆，即A^Y11（2.8 kbp）和A^Y9（750 bp）。通过使用cDNA作为问题的原位杂交结果表明，与A^Y11杂交的mRNA位于真皮细胞中（可见的肥大细胞），并且A^Y9的转录位点是黑素细胞。因此，A^Y11可能是A因子的cDNA，并且A^Y9是由A因子诱导的次级基因作用产物的cDNA。较少的