Essien F B, Haviland M B, Naidoff A E
Department of Biological Sciences, Rutgers University, New Brunswick, New Jersey 08855.
Teratology. 1990 Aug;42(2):183-94. doi: 10.1002/tera.1420420209.
A new autosomal mutation, Axd (axial defects), is described. Axd segregates in a simple Mendelian fashion, and it is dominant with incomplete penetrance and variable expressivity. The phenotype of Axd heterozygotes ranges from a variety of tail anomalies to visibly normal tails. Approximately 12% of neonates from curly-tail (CT) F1 (Axd/+) x F1 (Axd/+) matings exhibit open neural tube defects (NTD) in the lumbosacral region and 16% have curly tails. Mean litter sizes and resorption rates comparable to wild type indicate that homozygosity for Axd is not obligately lethal. Genetic background plays a major role in Axd expression. Strains such as BALB/cByJ allow the highest penetrance of the mutation in single dose (46%), whereas, in CF-1 mice Axd is recessive. The tail phenotype of heterozygous Axd/+ dams, in part reflective of their genetic background, correlates with the incidence of NTD in F2 offspring: CT mothers produce significantly more neonates with frank NTD than normal tail mothers. At the one embryonic period examined for this study (D13/D14 post-coitus), an 85% higher incidence of total axial defects is observed than among the F2 at birth. Unchanging litter size and the relative increase in phenotypically normal offspring by birth suggest that Axd acts by delaying posterior neural tube closure. One of the most significant findings in this study is that maternal age influences the survival of Axd embryos in utero. Axd/+ dams older than 8 months yield fewer mean implants, higher resorption rates, and fewer viable embryos with axial defects than do Axd/+ dams younger than 8 months. Axd is not allelic to nor linked to the Sp (splotch) gene which also affects neurulation.
描述了一种新的常染色体突变——Axd（轴向缺陷）。Axd以简单的孟德尔方式分离，呈显性遗传，具有不完全外显率和可变表达性。Axd杂合子的表型范围从各种尾部异常到外观正常的尾巴。来自卷尾（CT）F1（Axd/+）×F1（Axd/+）交配的新生儿中，约12%在腰骶部区域表现出开放性神经管缺陷（NTD），16%有卷尾。平均窝仔数和吸收发生率与野生型相当，表明Axd纯合子并非必然致死。遗传背景在Axd表达中起主要作用。诸如BALB/cByJ等品系单剂量时突变的外显率最高（46%），而在CF-1小鼠中Axd是隐性的。杂合子Axd/+母鼠的尾巴表型部分反映了它们的遗传背景，与F2代后代中NTD的发生率相关：CT母鼠所产有明显NTD的新生儿比正常尾巴母鼠多得多。在本研究检测的一个胚胎期（交配后第13/14天），观察到总轴向缺陷的发生率比出生时的F2代高85%。窝仔数不变以及出生时表型正常后代相对增加表明，Axd通过延迟神经管后闭合起作用。本研究中最显著的发现之一是，母龄影响Axd胚胎在子宫内的存活。8个月以上的Axd/+母鼠平均着床数较少、吸收发生率较高，且有轴向缺陷的存活胚胎比8个月以下的Axd/+母鼠少。Axd与同样影响神经胚形成的Sp（斑点）基因既非等位基因也不连锁。
