Tyson F L, Essien F B
Proc Natl Acad Sci U S A. 1985 Apr;82(7):2101-5. doi: 10.1073/pnas.82.7.2101.
Mouse fetuses homozygous for the lethal cab (cardiac abnormal) mutation are characterized by pleiotropic effects that lead to immediate postnatal death. Mutant fetuses have only 4% of the normal amount of hepatic glycogen and 39% of the normal cardiac glycogen reserve, coupled with lower specific activities of glycogen synthase and phosphorylase. Analysis with the periodic acid-Schiff reagent histochemical stain demonstrated that cab homozygotes also have reduced amounts of structural polysaccharides. One of the most distinctive mutant phenotypic traits is severe prenatal hypoglycemia, with average (+/-SEM) plasma glucose concentrations of 0.35 +/- 0.14 mM in late fetuses compared to 3.47 +/- 0.69 mM in normal littermates. Compromise of glucose transport from dam to fetus or altered cellular glucose utilization was considered as a possible basis for the low extracellular and intracellular (hepatic) levels of glucose in mutants. Transport of the glucose analogue alpha-methyl[14C]glucoside by the placenta of cab homozygotes is normal. However, metabolism of [14C]glucose by mutant cells yields only 20% of the normal amount of 14CO2. This reduced efficiency of glucose metabolism is correlated with lower ATP concentrations in mutant organs. Aberrant glucose utilization may account for the pleiotropic features of the cab syndrome.
致死性 cab（心脏异常）突变纯合子的小鼠胎儿具有多效性效应，导致出生后立即死亡。突变胎儿的肝糖原含量仅为正常量的 4%，心脏糖原储备为正常量的 39%，同时糖原合酶和磷酸化酶的比活性较低。用高碘酸 - 席夫试剂组织化学染色分析表明，cab 纯合子的结构多糖含量也减少。最显著的突变表型特征之一是严重的产前低血糖，晚期胎儿的平均（±SEM）血浆葡萄糖浓度为 0.35±0.14 mM，而正常同窝仔鼠为 3.47±0.69 mM。葡萄糖从母体向胎儿转运受损或细胞葡萄糖利用改变被认为是突变体中细胞外和细胞内（肝脏）葡萄糖水平低的可能原因。cab 纯合子胎盘对葡萄糖类似物α - 甲基[14C]葡萄糖苷的转运是正常的。然而，突变细胞对[14C]葡萄糖的代谢仅产生正常量 14CO2 的 20%。这种葡萄糖代谢效率降低与突变器官中较低的 ATP 浓度相关。异常的葡萄糖利用可能解释了 cab 综合征的多效性特征。
