Regardless of genotype, offspring of VIP-deficient female mice exhibit developmental delays and deficits in social behavior
Regardless of genotype, offspring of VIP-deficient female mice exhibit developmental delays and deficits in social behavior
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DOI：
10.1016/j.ijdevneu.2008.03.002
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发表时间：
2008-08-01
影响因子：
1.8
通讯作者：
Hill, Joanna M.
中科院分区：
文献类型：
--
作者：
Lim, Maria A.;Stack, Conor M.;Hill, Joanna M.
药理研究表明血管活性肠肽（VIP）可能是小鼠正常胚胎发育所必需的。例如，在胚胎期前使用VIP拮抗剂会导致发育迟缓、生长受限、改变成人脑化学物质和减少社会行为。本研究将VIP基因缺陷母（VIP +/-）与VIP +/+和+/-雄性交配的新生儿的发育里程碑、生长和社会行为与野生型母（VIP +/+）与VIP +/+和+/-雄性交配的后代进行比较，以评估母和后代VIP基因型的贡献。无论自身的基因型如何，vip缺陷母亲的所有后代都表现出发育迟缓。无论基因型如何，野生型母亲的后代都没有出现延迟。VIP缺乏母亲的后代体重显著下降，VIP无效（-/-）受影响最大。无论基因型如何，与野生型母亲的野生型后代相比，vip缺陷母亲的所有后代都表达了较低的母系亲缘关系；野生型母鼠的+/-后代与野生型幼崽的亲缘关系没有差异。vip缺乏母亲的所有后代的游戏行为都显著减少。野生型和vip缺陷型母鼠的母性行为没有差异，交叉饲养也没有改变后代的发育，表明后代缺陷是在产前引起的。本研究表明，孕鼠VIP基因型对子代生长发育和行为的影响大于子代自身VIP基因型。在vip缺乏母亲所生的+/+、+/-和-/-后代中，缺陷是明显的；正常母亲所生的+/-后代无明显缺陷。这些结果强调了子宫环境对正常发育的重要贡献，并表明VIP基因敲除小鼠在进一步了解具有社交行为缺陷的神经发育障碍（如自闭症）方面的潜在用途。由Elsevier Ltd代表ISDN出版。
Pharmacological studies indicate that vasoactive intestinal peptide (VIP) may be necessary for normal embryonic development in the mouse. For example, VIP antagonist treatment before embryonic day I I resulted in developmental delays, growth restriction, modified adult brain chemistry and reduced social behavior. Here, developmental milestones, growth, and social behaviors of neonates of VIP-deficient mothers (VIP +/-) mated to VIP +/- males were compared with the offspring of wild type mothers (VIP +/+) mated to VIP +/+ and +/- males, to assess the contributions of both maternal and offspring VIP genotype. Regardless of their own genotype, all offsprings of VIP-deficient mothers exhibited developmental delays. No delays were seen in the offspring of wild type mothers, regardless of their own genotype. Body weights were significantly reduced in offspring of VIP-deficient mothers, with VIP null (-/-) the most affected. Regardless of genotype, all offspring of VIP-deficient mothers expressed reduced maternal affiliation compared with wild type offspring of wild type mothers; +/- offspring of wild type mothers did not differ in maternal affiliation from their wild type littermates. Play behavior was significantly reduced in all offsprings of VIP-deficient mothers. Maternal behavior did not differ between wild type and VIP-deficient mothers, and cross-fostering of litters did not change offspring development, indicating that offspring deficits were induced prenatally. This study illustrated that the VIP status of a pregnant mouse had a greater influence on the growth, development and behavior of her offspring than the VIP genotype of the offspring themselves. Deficiencies were apparent in +/+, +/- and -/- offspring born to VIP-deficient mothers; no deficiencies were apparent in +/- offspring born to normal mothers. These results underscore the significant contribution of the uterine environment to normal development and indicate a potential usefulness of the VIP knockout mouse in furthering the understanding of neurodevelopmental disorders with social behavior deficits such as autism. Published by Elsevier Ltd on behalf of ISDN.