Haploinsufficiency of retinaldehyde dehydrogenase 2 decreases the severity and incidence of duodenal atresia in the fibroblast growth factor receptor 2IIIb-/- mouse model.
Haploinsufficiency of retinaldehyde dehydrogenase 2 decreases the severity and incidence of duodenal atresia in the fibroblast growth factor receptor 2IIIb-/- mouse model.
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DOI：
10.1016/j.surg.2012.07.022
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发表时间：
2012-10
期刊：
影响因子：
3.8
通讯作者：
Nichol, Peter F.
中科院分区：
文献类型：
--
作者：
Reeder, Amy L.;Botham, Robert A.;Zaremba, Krzysztof M.;Nichol, Peter F.
小鼠成纤维细胞生长因子受体 2IIIb (Fgfr2IIIb) 基因的纯合无效突变导致 42% 的胚胎出现十二指肠闭锁。视黄醛脱氢酶 2（Raldh2，一种对视黄酸生成至关重要的基因）在十二指肠闭锁形成的时间窗口期间在小鼠十二指肠中表达。 Raldh2 对于胰十二指肠区域的正常发育至关重要；因此，我们对 Raldh2 突变对十二指肠闭锁形成的影响感兴趣。为了测试这一点，我们使 Fgfr2IIIb−/− 胚胎的 Raldh2 单倍体不足，并检查这些胚胎十二指肠闭锁的发生率和严重程度。对照胚胎、Fgfr2IIIb−/− 突变体和 Fgfr2IIIb−/−； Raldh2+/- 突变体在胚胎第 18.5 天收获，进行基因分型，并固定过夜。分离肠道。记录十二指肠闭锁的类型和严重程度。总共研究了 97 个 Fgfr2IIIb−/− 胚胎； 44 例患有十二指肠闭锁，其中 41 例表现为 III 型。在 70 Fgfr2IIIb−/− 中；研究 Raldh2+/- 胚胎时，发现十二指肠闭锁的发生率较低（70 例中有 15 例；P = .0017；Fisher 精确检验）。闭锁的严重程度也降低了；有 12 个胚胎患有 I 型闭锁，3 个胚胎患有 II 型闭锁，0 个胚胎患有 III 型闭锁（P < 2.81E-013；Fisher 精确检验）。 Raldh2 的单倍体不足降低了 Fgfr2IIIb−/− 模型中十二指肠闭锁的发生率和严重程度。通过在特定遗传背景下操纵单个基因来改变缺陷严重程度的能力对于理解肠闭锁发生的机制具有潜在的重要意义。
Homozygous null mutation of the fibroblast growth factor receptor 2IIIb (Fgfr2IIIb) gene in mice results in 42% of embryos developing duodenal atresias. Retinaldehyde dehydrogenase 2 (Raldh2, a gene critical for the generation of retinoic acid) is expressed in the mouse duodenum during the temporal window when duodenal atresias form. Raldh2 is critical for the normal development of the pancreatoduodenal region; therefore, we were interested in the effect of a Raldh2 mutation on duodenal atresia formation. To test this, we rendered Fgfr2IIIb−/− embryos haploinsufficient for the Raldh2 and examined these embryos for the incidence and severity of duodenal atresia. Control embryos, Fgfr2IIIb−/− mutants, and Fgfr2IIIb−/−; Raldh2+/− mutants were harvested at embryonic day 18.5, genotyped, and fixed overnight. Intestinal tracts were isolated. The type and severity of duodenal atresia was documented. A total of 97 Fgfr2IIIb−/− embryos were studied; 44 had duodenal atresias, and 41 of these presented as type III. In the 70 Fgfr2IIIb−/−; Raldh2+/− embryos studied, a lesser incidence of duodenal atresia was seen (15 of 70; P = .0017; Fisher exact test). Atresia severity was also decreased; there were 12 embryos with type I atresias, 3 with type II atresias, and 0 with type III atresias (P < 2.81E–013; Fisher exact test). Haploinsufficiency of Raldh2 decreases the incidence and severity of duodenal atresia in the Fgfr2IIIb−/− model. The ability to alter defect severity through manipulation of a single gene in a specific genetic background has potentially important implications for understanding the mechanisms by which intestinal atresias arise.
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影响因子：
2.4
作者：
Nichol, Peter F.;Botham, Robert;Saijoh, Yukio;Reeder, Amy L.;Zaremba, Krzyztoff M.
通讯作者：
Zaremba, Krzyztoff M.
影响因子：
2.4
作者：
Fairbanks, TJ;Kanard, RC;Burns, RC
通讯作者：
Burns, RC
影响因子：
2.4
作者：
Botham RA;Franco M;Reeder AL;Lopukhin A;Shiota K;Yamada S;Nichol PF
通讯作者：
Nichol PF
影响因子：
2.4
作者：
Fairbanks, TJ;Sala, FG;Burns, RC
通讯作者：
Burns, RC
影响因子：
2.4
作者：
Fairbanks, TJ;Kanard, R;Burns, RC
通讯作者：
Burns, RC