Finnell R H, Moon S P, Abbott L C, Golden J A, Chernoff G F
Teratology. 1986 Apr;33(2):247-52. doi: 10.1002/tera.1420330213.
Neural tube defects are common congenital anomalies affecting approximately 0.1% of liveborn infants. It is widely accepted that these disorders are of a multifactorial origin, having both a genetic and an environmental component to their development. In a study designed to elucidate the genetic factors involved in a mouse model of hyperthermia-induced neural tube defects, it is apparent that a hierarchy of susceptibility exists among various inbred mouse strains. Female SWV mice were extremely sensitive to a 10-minute hyperthermic treatment on day 8.5 of gestation, with 44.3% of their offspring having exencephaly. The other strains used in these studies (LM/Bc, SWR/J, C57BL/6J, and DBA/2J) all had less than 14% affected offspring. In experimental situations where the environment is held constant and the only difference between the strains is their genotype, it is assumed that the difference in response to a teratogen is genetically mediated. To test the hypothesis that several genes are involved, reciprocal crosses were made between strains of high, moderate, and low sensitivity. When this was done, the high sensitivity of the SWV strain was lost in the F1 hybrid, implying not only that multiple genes are involved, but that it is the embryo's genotype and not the maternal genotype that is the major factor in determining susceptibility to heat-induced neural tube defects.
神经管缺陷是常见的先天性异常，影响约0.1%的活产婴儿。人们普遍认为，这些疾病起源于多因素，其发展既有遗传因素，也有环境因素。在一项旨在阐明高温诱导神经管缺陷小鼠模型中涉及的遗传因素的研究中，很明显，不同近交系小鼠品系之间存在易感性层次结构。雌性SWV小鼠在妊娠第8.5天对10分钟的高温处理极为敏感，其后代中有44.3%患有脑膨出。这些研究中使用的其他品系（LM/Bc、SWR/J、C57BL/6J和DBA/2J）受影响的后代均不到14%。在环境保持恒定且品系之间唯一差异在于其基因型的实验情况下，假定对致畸剂反应的差异是由基因介导的。为了检验涉及多个基因的假设，在高、中、低敏感性品系之间进行了正反交。当这样做时，SWV品系的高敏感性在F1杂种中消失了，这不仅意味着涉及多个基因，而且意味着决定对热诱导神经管缺陷易感性的主要因素是胚胎的基因型而非母体基因型。
