Wang Z Q, Fung M R, Barlow D P, Wagner E F
Research Institute for Molecular Pathology (I.M.P.), Vienna, Austria.
Nature. 1994 Dec 1;372(6505):464-7. doi: 10.1038/372464a0.
The receptor for insulin-like growth factor type 2, also known as the cation-independent mannose-6-phosphate receptor (Igf2/Mpr), is a multifunctional receptor thought to play a role in lysosomal targeting, cell growth and signal transduction. Igf2/Mpr has been mapped to the mouse Tme locus and shown to be an imprinted gene, which further suggests a role in embryonic growth regulation. To define the functions of Igf2/Mpr, we have generated mice lacking this gene. We report here that maternal inheritance of an Igf2/Mpr null allele (-/+) as well as homozygosity for the inactive allele (-/-) is generally lethal at birth and mutants are about 30% larger, indicating that maternal expression of Igf2/Mpr is essential for late embryonic development and growth regulation. The phenotype is probably caused by an excess of Igf2 because the introduction of an Igf2 null allele rescued the Igf2/Mpr mutant mice. Mutant mice also have organ and skeletal abnormalities and missort mannose-6-phosphate-tagged proteins. A few (-/+) mice reactivated their paternal Igf2/Mpr allele in some tissues and survived to adults. But no (-/-) mice survived, indicating a role for the reactivated paternal allele in postnatal survival.
胰岛素样生长因子2型受体，也被称为不依赖阳离子的甘露糖-6-磷酸受体（Igf2/Mpr），是一种多功能受体，被认为在溶酶体靶向、细胞生长和信号转导中发挥作用。Igf2/Mpr已被定位到小鼠的Tme位点，并被证明是一个印记基因，这进一步表明其在胚胎生长调节中发挥作用。为了确定Igf2/Mpr的功能，我们培育出了缺乏该基因的小鼠。我们在此报告，Igf2/Mpr无效等位基因（-/+）的母系遗传以及无效等位基因的纯合性（-/-）在出生时通常是致命的，突变体大约大30%，这表明Igf2/Mpr的母系表达对于胚胎后期发育和生长调节至关重要。这种表型可能是由于Igf2过量导致的，因为引入Igf2无效等位基因挽救了Igf2/Mpr突变小鼠。突变小鼠还存在器官和骨骼异常，并且甘露糖-6-磷酸标记的蛋白质分选错误。一些（-/+）小鼠在某些组织中重新激活了其父亲的Igf2/Mpr等位基因并存活至成年。但没有（-/-）小鼠存活下来；这表明重新激活的父本等位基因在出生后存活中发挥了作用。
