Abstract
Recent outbreaks of infectious neuro-developmental diseases such as congenital Zika syndrome - have led to a demand for prognosis data from animal models. We developed an intra-amniotic injection mice model that allows Zika virus (ZIKV) infected mice to grow to puberty. In this system, ZIKV is injected into the amniotic fluid of pregnant mice and infected embryos thereafter. ZIKV-infected mice show several symptoms of clinical ‘congenital Zika syndrome’, including decreased brain volume and mis-laminated retina. We also evaluated several behavioral functions of these ZIKV-infected mice, for example, after the mice reach puberty, they have visual and motor defects. This technique can be used to screen and evaluate drug candidates and may help evaluate the prognosis of infectious neuro-developmental diseases.
Keywords: Intra-amniotic, Embryos, Virus, Infection
Background
It has been more than sixty years since the first human case of ZIKV infection was reported but in 2007 only 14 human cases of ZIKV infection had been recorded. Prognosis data have lagged far behind the recent outbreak of ZIKV in 2015. There is some evidence that mouse models may be effective for prognosis studies because previous reports have proved neurovirulence of ZIKV in mice. Therefore, various methods of ZIKV infection including intravenous injection, intraperitoneal injection, foot-pad injection and brain injection have been used to study congenital Zika syndrome in individuals during the embryonic period or infancy. The intra-amniotic injection model presented here has two advantageous features. First, wild-type mice (C57 BL/6J) can be used and studies are not limited to mice with immunologic deficiencies. Second, ZIKV infected mice can grow into puberty, which is beneficial to studies trying to evaluate prognosis.
Materials and Reagents
Equipment
Procedure
Data analysis
Analysis of behavioral tests including open filed test, tail suspension test, rota-rod test, catwalk and elevated plus maze in the visual and motor deficits of ZIKV infected mice can be found online at http://www.ebiomedicine.com/article/S2352-3964(17)30184-6/fulltext#s0010.
Notes
Recipes
Acknowledgments
The authors declare no competing interests. This protocol was adapted from Cui et al. (2017). J.Z. thanks the following funding agencies for supporting this work: the NSF of China (31771195, 81790640), the Young 1000 Plan and Ministry of Science and Technology of the People’s Republic of China (2015AA020512). L. L. thanks the following funding agencies for supporting this work: Ministry of Science and Technology of the People’s Republic of China (2015AA020930 and 2016YFC1202901).
References
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