Franke Barbara, Klootwijk Riko, Lemmers Bianca, de Kovel Carolien G F, Steegers-Theunissen Regine P M, Mariman Edwin C M
Department of Human Genetics, University Medical Center Nijmegen, Nijmegen, The Netherlands.
Birth Defects Res A Clin Mol Teratol. 2003 Dec;67(12):979-84. doi: 10.1002/bdra.10132.
Bent tail is a mouse model for X-linked neural tube defects (NTDs) that is characterized by the presence of exencephaly, a delayed posterior neuropore closure, and a tail phenotype. In addition, Bent tail shows laterality defects and increased prenatal mortality. The congenital malformations of this mouse are caused by a submicroscopic deletion that completely encompasses the gene coding for the zinc finger transcription factor Zic3. In this study we investigated the sensitivity of the phenotype of Bent tail to the nutrients folinic acid, myo-inositol, and zinc. These nutrients are thought to be involved in the etiology of NTDs, in combination with a genetic predisposition.
The most penetrant phenotype of the Bent tail mouse, the tail malformation, was used as a marker for the nutrient sensitivity of the neural phenotype. The size of the litters and the survival of the offspring, subdivided according to genotype, were analyzed as markers for the nutrient sensitivity of other phenotypic features of Bent tail.
In confirmation of earlier studies, we observed the prenatal loss of a number of homozygous females and hemizygous males, as well as the effect of genotype on the tail phenotype of Bent tail. However, periconceptional supplementation of the maternal diet with folinic acid, myo-inositol, or zinc produced no significant effects on either the tail phenotype of the offspring or the size and genotypic composition of the litters.
Bent tail appears to be a folinic acid-, myo-inositol-, and zinc-insensitive mouse model for NTDs.
弯尾小鼠是一种X连锁神经管缺陷（NTDs）的小鼠模型，其特征为无脑畸形、后神经孔闭合延迟以及尾巴表型异常。此外，弯尾小鼠还表现出身体侧化缺陷和产前死亡率增加。该小鼠的先天性畸形是由一个亚显微缺失引起的，该缺失完全包含了编码锌指转录因子Zic3的基因。在本研究中，我们调查了弯尾小鼠表型对亚叶酸、肌醇和锌等营养素的敏感性。这些营养素被认为与NTDs的病因有关，且与遗传易感性相关。
弯尾小鼠最显著的表型，即尾巴畸形，被用作神经表型对营养素敏感性的标志物。根据基因型对窝仔大小和后代存活率进行分析，作为弯尾小鼠其他表型特征对营养素敏感性的标志物。
正如早期研究所证实的，我们观察到许多纯合雌性和半合子雄性小鼠在产前死亡，以及基因型对弯尾小鼠尾巴表型的影响。然而，在受孕前后给母鼠饮食补充亚叶酸、肌醇或锌，对后代的尾巴表型或窝仔大小及基因型组成均无显著影响。
弯尾小鼠似乎是一种对亚叶酸、肌醇和锌不敏感的NTDs小鼠模型。
