Bennett Gregory D, Vanwaes Janee, Moser Kristine, Chaudoin Tammy, Starr Lois, Rosenquist Thomas H
Department of Genetics Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, Nebraska 68198-5805, USA.
Birth Defects Res B Dev Reprod Toxicol. 2006 Apr;77(2):89-94. doi: 10.1002/bdrb.20071.
Folate deficiencies have been associated with many adverse congenital abnormalities. It is not clear, however, whether these defects are due to a folate deficiency or to an increase in homocysteine. Homocysteine has been shown to be teratogenic in the chicken-embryo model and it has been suggested that homocysteine-induced defects are mediated by inhibiting the N-methyl-D-aspartate (NMDA) receptor on neural crest cells. The majority of the teratology studies have been carried out using the chicken embryo model. In an effort to develop a murine model of homocysteine-induced neural tube defects, several inbred mouse strains were treated with homocysteine or the NMDA inhibitor MK801 and the fetuses examined for any induced-NTD.
Several in-bred mouse strains were administered homocysteine once on gestational day (GD) E8.5 or once daily on GD 6.5-10.5. Additionally, because homocysteine was been reported to mediate its effects through the NMDA receptor, the effect of MK801, an antagonist of this receptor, was also investigated.
Regardless of the mouse treatment time, homocysteine failed to induce neural tube defects in our in-bred mouse strains. Homocysteine also failed to increase the number of neural tube defects in the splotch strain, regardless of the genotype.
Irrespective of the mouse strain or treatment, homocysteine failed to induce neural tube defects in our mouse models, which is in contrast to what has been reported in the chicken embryo models.
叶酸缺乏与许多不良先天性异常有关。然而，尚不清楚这些缺陷是由于叶酸缺乏还是同型半胱氨酸增加所致。同型半胱氨酸在鸡胚模型中已被证明具有致畸性，有人提出同型半胱氨酸诱导的缺陷是通过抑制神经嵴细胞上的N-甲基-D-天冬氨酸（NMDA）受体介导的。大多数致畸学研究是使用鸡胚模型进行的。为了建立同型半胱氨酸诱导神经管缺陷的小鼠模型，用同型半胱氨酸或NMDA抑制剂MK801处理了几种近交系小鼠，并检查胎儿是否有诱导性神经管缺陷。
在妊娠第（GD）E8.5天对几种近交系小鼠给药一次同型半胱氨酸，或在GD 6.5 - 10.5天每天给药一次。此外，由于据报道同型半胱氨酸通过NMDA受体介导其作用，还研究了该受体拮抗剂MK801的作用。
无论小鼠的处理时间如何，同型半胱氨酸均未能在我们的近交系小鼠中诱导神经管缺陷。无论基因型如何，同型半胱氨酸也未能增加斑点品系中的神经管缺陷数量。
无论小鼠品系或处理方式如何，同型半胱氨酸均未能在我们的小鼠模型中诱导神经管缺陷，这与鸡胚模型中的报道相反。
