Stabilin2 (Stab2) encodes a large transmembrane protein which is predominantly expressed in the liver sinusoidal endothelial cells (LSECs) and functions as a scavenger receptor for various macromolecules including hyaluronans (HA). In DBA/2J mice, plasma HA concentration is ten times higher than in 129S6 or C57BL/6J mice, and this phenotype is genetically linked to the Stab2 locus. Stab2 mRNA in the LSECs was significantly lower in DBA/2J than in 129S6, leading to reduced STAB2 proteins in the DBA/2J LSECs. We found a retrovirus-derived transposable element, intracisternal A particle (IAP), in the promoter region of Stab2DBA which likely interferes with normal expression in the LSECs. In contrast, in other tissues of DBA/2J mice, the IAP drives high ectopic Stab2DBA transcription starting within the 5' long terminal repeat of IAP in a reverse orientation and continuing through the downstream Stab2DBA. Ectopic transcription requires the Stab2-IAP element but is dominantly suppressed by the presence of loci on 59.7-73.0 Mb of chromosome (Chr) 13 from C57BL/6J, while the same region in 129S6 requires additional loci for complete suppression. Chr13:59.9-73 Mb contains a large number of genes encoding Krüppel-associated box-domain zinc-finger proteins that target transposable elements-derived sequences and repress their expression. Despite the high amount of ectopic Stab2DBA transcript in tissues other than liver, STAB2 protein was undetectable and unlikely to contribute to the plasma HA levels of DBA/2J mice. Nevertheless, the IAP insertion and its effects on the transcription of the downstream Stab2DBA exemplify that stochastic evolutional events could significantly influence susceptibility to complex but common diseases.

中文翻译：

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Stabilin2基因在小鼠DBA / 2J株中由脑池内A粒子（IAP）元素触发的异位表达。

Stabilin2（Stab2）编码一种大型跨膜蛋白，主要在肝窦窦内皮细胞（LSECs）中表达，并充当各种透明质酸（HA）的大分子清除剂。在DBA / 2J小鼠中，血浆HA浓度比129S6或C57BL / 6J小鼠高十倍，并且该表型与Stab2基因座遗传相关。在LSEC中，DBA / 2J中的Stab2 mRNA显着低于129S6，导致DBA / 2J LSEC中的STAB2蛋白减少。我们在Stab2DBA的启动子区域中发现了逆转录病毒衍生的转座元件，脑池内A颗粒（IAP），这很可能会干扰LSECs的正常表达。相反，在DBA / 2J小鼠的其他组织中，IAP从5'内开始驱动异位的Stab2DBA转录 IAP的长末端重复，方向相反，并持续通过下游Stab2DBA。异位转录需要Stab2-IAP元件，但被C57BL / 6J染色体（Chr）13的59.7-73.0 Mb上基因座的存在显着抑制，而129S6中的相同区域需要额外的基因座才能完全被抑制。Chr13：59.9-73 Mb包含大量编码Krüppel相关框域锌指蛋白的基因，这些基因靶向可转座因子衍生的序列并抑制其表达。尽管在除肝脏以外的组织中存在大量异位Stab2DBA转录物，但STAB2蛋白却无法检测到，并且不太可能导致DBA / 2J小鼠的血浆HA水平升高。不过，