Brown G D, Choi Y, Egan G, Meruelo D
Department of Pathology, New York University Medical Center, NY 10016.
Immunogenetics. 1988;27(4):239-51. doi: 10.1007/BF00376118.
A region of the TLb locus encompassing T11 to T13 contains retroviral sequences TLev1 and TLev2. As part of a study to determine whether the retroviral elements are involved in the expression of TL genes, the genomic organization of this region was reexamined in greater detail. A result of these investigations is the extension of the H-2 TLb molecular map. Two additional TL genes have been isolated from C57BL/6 mice, T14 and T15. The genomic organization of T9 through T15 is presented. The nucleotide sequence has been determined for exons 4, 5, and 6 of T13. As a result of a C to T conversion, a termination codon is introduced into exon 4, indicating that T13 either encodes a secreted protein or is a pseudogene. T13 was found to be more homologous to the H-2 genes outside the TL region. T14 has been physically disrupted by the integration of TLev1, and the H-2 sequences appear to have diverged greatly. The relationship of the TL regions of the b and c haplotypes has been investigated using numerous low copy probes. The genome of BALB/c (TLc) is shown to lack a counterpart of the T13-T15b region. Homologous regions exist in the two haplotypes; yet considerable polymorphism is observed. TLb mice do not express TLa on the cell surface of normal thymocytes while TLc mice do; TLa expression is activated in many TLb leukemias. The diversity seen in the T13-T15 region may provide insights into the phenotypic expression or regulatory mechanisms of TL expression in these two haplotypes.
TLb基因座中包含T11至T13的区域含有逆转录病毒序列TLev1和TLev2。作为确定逆转录病毒元件是否参与TL基因表达的研究的一部分，对该区域的基因组组织进行了更详细的重新检查。这些研究的一个结果是扩展了H-2 TLb分子图谱。从C57BL/6小鼠中分离出另外两个TL基因，T14和T15。展示了T9至T15的基因组组织。已确定T13外显子4、5和6的核苷酸序列。由于C到T的转换，一个终止密码子被引入外显子4，这表明T13要么编码一种分泌蛋白，要么是一个假基因。发现T13与TL区域外的H-2基因更同源。T14因TLev1的整合而在物理上被破坏，并且H-2序列似乎已经有了很大的分歧。使用多种低拷贝探针研究了b和c单倍型的TL区域之间的关系。结果表明，BALB/c（TLc）的基因组缺乏T13 - T15b区域的对应物。两种单倍型中存在同源区域；然而观察到相当大的多态性。TLb小鼠在正常胸腺细胞的细胞表面不表达TLa，而TLc小鼠则表达；在许多TLb白血病中TLa表达被激活。在T13 - T15区域中看到的多样性可能为这两种单倍型中TL表达的表型表达或调控机制提供见解。
