The herpes simplex virus type 1 thymidine kinase is expressed in the testes of transgenic mice under the control of a cryptic promoter
The herpes simplex virus type 1 thymidine kinase is expressed in the testes of transgenic mice under the control of a cryptic promoter
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单纯疱疹病毒 1 型胸苷激酶在隐性启动子的控制下在转基因小鼠的睾丸中表达
DOI：
10.1128/mcb.11.8.4207-4216.1991
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发表时间：
1991
影响因子：
5.3
通讯作者：
John O. Bishop
中科院分区：
文献类型：
--
作者：
Raya Al;J. Burke;H. Wallace;C. Jones;S. Harrison;D. Buxton;S. Maley;A. Chandley;John O. Bishop
我们以前报道过，单纯疱疹病毒1型（HSV-1）胸苷激酶报告基因（tk）在转基因小鼠的睾丸中表达时，耦合到肝脏特异性小鼠主要尿蛋白（MUP）基因的启动子。在这里，我们表明，HSV-1 TK也在睾丸中表达时，耦合到MUP假基因启动子，截短的MUP启动子，在肝脏中没有活性，和牛甲状腺球蛋白基因的启动子。此外，HSV-1 tk本身在睾丸中表达，尽管通过去除上游转录调节因子使其正常表达失效。在每种情况下，观察到相同的多个转录物，其5'端位于正常HSV-1 tk翻译起始密码子的下游。我们的结论是，HSV-1 tk在睾丸中的转录是由一个隐蔽的TATA盒独立的启动子位于该基因的编码区。在睾丸中合成的最长的HSV-1胸苷激酶（TK）多肽短于全长TK，可能是由tk阅读框架的第二和第三个ATG密码子Met 46和Met 60的翻译起始引起的。大多数转基因品系的雄性小鼠不育，精子发生损伤的严重程度与TK表达水平直接相关。在最高表达的品系中，精子计数较低，形态缺陷精子很常见。在其他不育系中，TK的表达水平较低，精子数量正常，但精子活力大大降低。具有最低水平的HSV-1 TK表达的品系是可育的。HSV-1 TK在生殖细胞中表达，主要在单倍体精子细胞中表达。然而，在第一个生殖细胞进入减数分裂之前，在睾丸中发现了低水平的HSV-1 TK活性，表明如果表达仅限于生殖细胞，则其也发生在精原细胞中。
We reported previously that the herpes simplex virus type 1 (HSV-1) thymidine kinase reporter gene (tk) was expressed in the testes of transgenic mice when coupled to the promoter of a liver-specific mouse major urinary protein (MUP) gene. Here we show that HSV-1 tk is also expressed in the testis when coupled to a MUP pseudogene promoter, to a truncated MUP promoter that is not active in the liver, and to the promoter of the bovine thyroglobulin gene. Furthermore, HSV-1 tk itself was expressed in the testis, although its normal expression had been disabled by removing an upstream regulator of transcription. In every case, the same multiple transcripts were observed, with their 5' ends located downstream of the normal HSV-1 tk translation initiation codon. We conclude that the transcription of HSV-1 tk in the testis is directed by a cryptic TATA box-independent promoter located in the coding region of the gene. The longest HSV-1 thymidine kinase (TK) polypeptides synthesized in the testis were shorter than full-length TK and probably result from translational initiation at Met46 and Met60, the second and third ATG codons of the tk reading frame. Male mice of most transgenic lines were sterile, and the severity of the lesion in spermatogenesis was directly related to the level of TK expression. In the most highly expressing lines, sperm counts were low and morphologically defective sperm were common. In other sterile lines, TK was expressed at a lower level and sperm counts were normal but sperm motility was greatly reduced. Lines with the lowest levels of HSV-1 TK expression were fertile. HSV-1 TK was expressed in germ line cells, mainly in the haploid spermatids. However, low-level HSV-1 TK activity was found in the testis before the first germ cells entered meiosis, showing that if expression is confined to the germ cells, it also occurs in spermatogonia.
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DOI：
10.1073/pnas.86.8.2698
发表时间：
1989-04-01
影响因子：
11.1
作者：
HEYMAN, RA;BORRELLI, E;EVANS, RM
通讯作者：
EVANS, RM
影响因子：
3.7
作者：
HECHT, NB;BOWER, PA;DISTEL, RJ
通讯作者：
DISTEL, RJ
大鼠细胞色素 c 氧化酶亚基 IV 基因家族：亚基 IV 和细胞色素 c mRNA 表达的组织特异性和激素差异。
影响因子：
14.9
作者：
Virbasius,JV;Scarpulla,RC
通讯作者：
Scarpulla,RC
影响因子：
3.7
作者：
IRMIERE, AF;MANOS, MM;COEN, DM
通讯作者：
COEN, DM
DOI：
10.1073/pnas.84.15.5316
发表时间：
1987-08-01
影响因子：
11.1
作者：
PESCHON, JJ;BEHRINGER, RR;PALMITER, RD
通讯作者：
PALMITER, RD