Compensatory upregulation of myelin protein zero-like 2 expression in spermatogenic cells in cell adhesion molecule-1-deficient mice.

Compensatory upregulation of myelin protein zero-like 2 expression in spermatogenic cells in cell adhesion molecule-1-deficient mice.
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DOI:
10.1267/ahc.11057
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发表时间:
2012-02-29
影响因子:
2.4
通讯作者:
Iseki S
Iseki S
中科院分区:
生物学4区
文献类型:
--
作者:
Nakata H;Wakayama T;Adthapanyawanich K;Nishiuchi T;Murakami Y;Takai Y;Iseki S

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细胞粘附分子-1(Cadm 1)是免疫球蛋白超家族的成员。在小鼠睾丸中,Cadm 1在早期生精细胞到粗线期早期精母细胞中表达,也在细长的精子细胞中表达,但在Sertoli细胞中不表达。Cadm 1缺陷小鼠由于精子发生缺陷而具有雄性不育,其中精子细胞的分离是突出的,而精母细胞看起来是完整的。为了阐明由Cadm 1缺陷引起的精子发生受损的分子机制,我们进行了DNA微阵列分析的全球基因表达在睾丸Cadm 1缺陷和野生型小鼠之间的比较。在Cadm 1缺陷小鼠中上调的25个基因中,我们对髓磷脂蛋白零样2(Mpzl 2)特别感兴趣,这是免疫球蛋白超家族的另一种细胞粘附分子。用定量PCR和蛋白质印迹法分别分析,在Cadm 1缺陷小鼠的睾丸中,Mpzl 2 mRNA的水平增加了20倍,Mpzl 2蛋白的水平增加了2倍。原位杂交和免疫组化表明,Mpzl 2 mRNA和蛋白质定位于早期的生精细胞,但不是在细长的精子细胞或Sertoli细胞,在野生型和Cadm 1缺陷小鼠。这些结果表明,Mpzl 2可以弥补早期生精细胞中Cadm 1的缺陷。
The cell adhesion molecule-1 (Cadm1) is a member of the immunoglobulin superfamily. In the mouse testis, Cadm1 is expressed in the earlier spermatogenic cells up to early pachytene spermatocytes and also in elongated spermatids, but not in Sertoli cells. Cadm1-deficient mice have male infertility due to defective spermatogenesis, in which detachment of spermatids is prominent while spermatocytes appear intact. To elucidate the molecular mechanisms of the impaired spermatogenesis caused by Cadm1 deficiency, we performed DNA microarray analysis of global gene expression in the testis compared between Cadm1-deficient and wild-type mice. Out of the 25 genes upregulated in Cadm1-deficient mice, we took a special interest in myelin protein zero-like 2 (Mpzl2), another cell adhesion molecule of the immunoglobulin superfamily. The levels of Mpzl2 mRNA increased by 20-fold and those of Mpzl2 protein increased by 2-fold in the testis of Cadm1-deficient mice, as analyzed with quantitative PCR and western blotting, respectively. In situ hybridization and immunohistochemistry demonstrated that Mpzl2 mRNA and protein are localized in the earlier spermatogenic cells but not in elongated spermatids or Sertoli cells, in both wild-type and Cadm1-deficient mice. These results suggested that Mpzl2 can compensate for the deficiency of Cadm1 in the earlier spermatogenic cells.
DOI: 10.1128/mcb.26.9.3610-3624.2006
发表时间: 2006-05-01
影响因子: 5.3
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