Embryonic Survival and Severity of Cardiac and Craniofacial Defects Are Affected by Genetic Background in Fibroblast Growth Factor-16 Null Mice
Embryonic Survival and Severity of Cardiac and Craniofacial Defects Are Affected by Genetic Background in Fibroblast Growth Factor-16 Null Mice
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DOI：
10.1089/dna.2010.1024
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发表时间：
2010-08-01
影响因子：
3.1
通讯作者：
Cattini, Peter A.
中科院分区：
文献类型：
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作者：
Lu, Shun Yan;Jin, Yan;Cattini, Peter A.
在两项独立的研究中，X染色体成纤维细胞生长因子16（FGF-16）基因（FGF-9亚家族的一员）与FGF-20的破坏与心脏发育的影响有关。然而，在胚胎第11.5天（E），具有致死性的小梁形成不良仅与一种相关，涉及在瑞士黑鼠（Bsw）与C57 BL/6小鼠中的维持。本研究的目的是检查潜在的影响，遗传背景，通过育种无效突变到一个替代（C57 BL/6）的背景。三代后，25%的Fgf-16（-/Y）小鼠存活至成年，这可以通过与另一品系回交减少C57 BL/6遗传背景的贡献来逆转。无论品系如何，Fgf-16缺失小鼠与野生型小鼠中FGF-9和FGF-20 RNA水平之间没有显著差异。然而，FGF-8 RNA水平在Bsw而不是C57 BL/6小鼠中显著降低。FGF-8与前心脏发育有关，并且与FGF-9亚家族一样，据报道在E10.5表达。与FGF-16一样，神经调节蛋白以及通过ErbB 2和ErbB 4受体的信号传导与E10.5左右的小梁形成和心脏发育有关。Bsw与C57 BL/6小鼠的基础神经调节蛋白、ErbB 2和ErbB 4以及FGF-8、FGF-9和FGF-16 RNA水平不同。这些数据与遗传背景改变表型并影响Fgf-16缺失小鼠胚胎存活的能力一致。
Disruption of the X-chromosome fibroblast growth factor 16 (Fgf-16) gene, a member of the FGF-9 subfamily with FGF-20, was linked with an effect on cardiac development in two independent studies. However, poor trabeculation with lethality by embryonic day (E) 11.5 was associated with only one, involving maintenance in Black Swiss (Bsw) versus C57BL/6 mice. The aim of this study was to examine the potential influence of genetic background through breeding the null mutation onto an alternate (C57BL/6) background. After three generations, 25% of Fgf-16(-/Y) mice survived to adulthood, which could be reversed by reducing the contribution of the C57BL/6 genetic background by back crossing to another strain. There was no significant difference between FGF-9 and FGF-20 RNA levels in Fgf-16 null versus wild-type mice regardless of strain. However, FGF-8 RNA levels were reduced significantly in Bsw but not C57BL/6 mice. FGF-8 is linked to anterior heart development and like the FGF-9 subfamily is reportedly expressed at E10.5. Like FGF-16, neuregulin as well as signaling via ErbB2 and ErbB4 receptors have been linked to trabeculae formation and cardiac development around E10.5. Basal neuregulin, ErbB2, and ErbB4 as well as FGF-8, FGF-9, and FGF-16 RNA levels varied in Bsw versus C57BL/6 mice. These data are consistent with the ability of genetic background to modify the phenotype and affect embryonic survival in Fgf-16 null mice.