Pde6b rd1 mutation modifies cataractogenesis in Foxe3 rct mice
Pde6b rd1 mutation modifies cataractogenesis in Foxe3 rct mice
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Pde6b rd1 突变改变 Foxe3 rct 小鼠的白内障发生
DOI：
10.1016/j.bbrc.2018.01.031
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发表时间：
2018
影响因子：
3.1
通讯作者：
Kikkawa Yoshiaki
中科院分区：
文献类型：
--
作者：
Wada Kenta;Saito Junichi;Yamaguchi Midori;Seki Yuta;Furugori Masamune;Takahashi Gou;Nishito Yasumasa;Matsuda Hiroshi;Shitara Hiroshi;Kikkawa Yoshiaki
Foxe 3rct突变是在SJL/J小鼠中发现的一种隐性突变，可导致早发性白内障。先前的一项研究报道，白内障表型被小鼠近交系的遗传背景修饰，并且诱导感光细胞变性的Pde 6 brd 1突变是加速Foxe 3rct小鼠白内障发生严重程度的强有力的候选遗传修饰剂。我们通过将包含Foxe 3rct突变的基因组区域转移到不携带Pde 6 brd 1突变的B6遗传背景中来创建同源小鼠。在同类小鼠中，白内障表型变得非常轻微，并且白内障的发展被长时间抑制。此外，我们通过将包括野生型Pde 6 b基因的BAC克隆注射到SJL-Foxe 3rct小鼠的卵中来创建转基因小鼠。虽然转基因小鼠对白内障表型的抗性效果低于同类小鼠，但与原始SJL-Foxe 3rct小鼠的表型相比，白内障表型的严重程度和发病时间分别明显改善和延迟。这些结果清楚地表明，早发性白内障的发生需要至少两个突变等位基因Foxe 3rct和Pde 6 brd 1，另一个修饰与白内障表型的严重程度在Foxe 3rct小鼠的遗传背景的基础。
TheFoxe3rctmutation, which causes early-onset cataracts, is a recessive mutation found in SJL/J mice. A previous study reported that cataract phenotypes are modified by the genetic background of mouse inbred strains and that thePde6brd1mutation, which induced degeneration of the photoreceptor cells, is a strong candidate genetic modifier to accelerate the severity of cataractogenesis ofFoxe3rctmice. We created congenic mice by transferring a genomic region including theFoxe3rctmutation to the B6 genetic background, which does not carry thePde6brd1mutation. In the congenic mice, the cataract phenotypes became remarkably mild, and the development of cataracts was suppressed for a long time. Moreover, we created transgenic mice by injecting BAC clones including the wild-typePde6bgene into the eggs of SJL-Foxe3rctmice. Although the resistant effect for cataract phenotypes in transgenic mice was less than that in congenic mice, the severity and onset time of cataract phenotypes were clearly improved and delayed, respectively, compared with the phenotypes of the original SJL-Foxe3rctmice. These results clearly show that the development of early-onset cataracts requires at least two mutant alleles ofFoxe3rctandPde6brd1, and another modifier associated with the severity of cataract phenotypes inFoxe3rctmice underlies the genetic backgrounds in mice.