Tgfbeta2 -/- Tgfbeta3 -/- double knockout mice display severe midline fusion defects and early embryonic lethality.
Tgfbeta2 -/- Tgfbeta3 -/- double knockout mice display severe midline fusion defects and early embryonic lethality.
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发表时间：
2002
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通讯作者：
N. Dünker;K. Krieglstein
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作者：
N. Dünker;K. Krieglstein
鉴于所有已知的生物活性，预期转化生长因子β（TGF-β）在许多不同的发育过程中发挥重要作用。由于所有三种TGF-β同种型显示重叠的表达模式，一种TGF-β同种型的缺失可能会被另一种所补偿。在本研究中，进行了Tgf β 2和Tgf β 3基因的靶向破坏，以规避这个问题，并确定TGF-β 2和TGF-β 3在体内的重要作用。Tgf β 2（-/-）Tgf β 3（-/-）双基因敲除小鼠及其三等位基因Tgf β 2（-/-）Tgf β 3（+/-）同窝小鼠显示肋骨远端部分缺失、胸骨原基缺失和腹体壁闭合失败，导致心脏位于胸外位置和肝脏突出。此外，还观察到结缔组织组成异常和早期胚胎死亡[约胚胎日（E）15.5]。相反，Tgf β 2（+/-）Tgf β 3（-/-）同窝仔显示肋骨和胸骨发育正常，前体壁融合正常，并且在E18.5时仍然存活。已知TGF-β 2在骨骼和颅面发育中发挥作用。结果表明，除此之外：（a）。TGF-β明显在中线融合和（B）中起重要作用。Tgf β 2基因似乎在介导发育过程中比Tgf β 3基因起更重要的作用，因为Tgf β 2（+/-）Tgf β 3（-/-）突变体-与它们的Tgf β 2（-/-）Tgf β 3（+）（/-）同窝仔相反-不显示严重的畸形。
Given all known biological activities, it is anticipated that transforming growth factors beta (TGF-betas) play important roles in many different developmental processes. As all three TGF-beta isoforms display overlapping expression patterns, deletion of one TGF-beta isoform might be compensated for by another. In the present study, targeted disruption of both Tgfbeta2 and Tgfbeta3 genes was undertaken to circumvent this problem and determine the essential roles of TGF-beta2 and TGF-beta3 in vivo. Tgfbeta2(-/-) Tgfbeta3(-/-) double knockout mice and their three-allelic Tgfbeta2(-/-) Tgfbeta3(+/-) littermates display a lack of distal parts of the rib, a lack of sternal primordia, and failure in ventral body wall closure, leading to an extrathoracic position of the heart and extrusion of the liver. In addition, abnormalities in connective tissue composition and an early embryonic lethality [around embryonic day (E) 15.5] are seen. In contrast, Tgfbeta2 (+/-) Tgfbeta3 (-/-) littermates show normal rib and sternum development, normal anterior body wall fusion, and are still alive on E18.5. TGF-beta2 is already known to play a role in skeletal and craniofacial development. The results presented here show that beyond this: (a). TGF-betas obviously play a fundamental role in midline fusion and (b). the Tgfbeta2 gene seems to play a more important role in mediating developmental processes than the Tgfbeta3 gene, since Tgfbeta2 (+/-) Tgfbeta3 (-/-) mutants - in contrast to their Tgfbeta2(-/-) Tgfbeta3 (+)(/-) littermates - do not display severe malformations.