Liu J P, Baker J, Perkins A S, Robertson E J, Efstratiadis A
Department of Genetics and Development, Columbia University, New York, New York 10032.
Cell. 1993 Oct 8;75(1):59-72.
Newborn mice homozygous for a targeted disruption of insulin-like growth factor gene (Igf-1) exhibit a growth deficiency similar in severity to that previously observed in viable Igf-2 null mutants (60% of normal birthweight). Depending on genetic background, some of the Igf-1(-/-) dwarfs die shortly after birth, while others survive and reach adulthood. In contrast, null mutants for the Igf1r gene die invariably at birth of respiratory failure and exhibit a more severe growth deficiency (45% normal size). In addition to generalized organ hypoplasia in Igf1r(-/-) embryos, including the muscles, and developmental delays in ossification, deviations from normalcy were observed in the central nervous system and epidermis. Igf-1(-/-)/Igf1r(-/-) double mutants did not differ in phenotype from Igf1r(-/-) single mutants, while in Igf-2(-)/Igf1r(-/-) and Igf-1(-/-)/Igf-2(-) double mutants, which are phenotypically identical, the dwarfism was further exacerbated (30% normal size). The roles of the IGFs in mouse embryonic development, as revealed from the phenotypic differences between these mutants, are discussed.
胰岛素样生长因子基因（Igf-1）靶向破坏的纯合新生小鼠表现出与之前在存活的Igf-2基因敲除突变体中观察到的严重程度相似的生长缺陷（正常出生体重的60%）。根据遗传背景，一些Igf-1(-/-)侏儒在出生后不久死亡，而其他则存活并成年。相比之下，Igf1r基因的敲除突变体总是在出生时死于呼吸衰竭，并表现出更严重的生长缺陷（正常大小的45%）。除了Igf1r(-/-)胚胎中包括肌肉在内的全身器官发育不全以及骨化发育延迟外，在中枢神经系统和表皮中也观察到了与正常情况的偏差。Igf-1(-/-)/Igf1r(-/-)双突变体在表型上与Igf1r(-/-)单突变体没有差异，而在表型相同的Igf-2(-)/Igf1r(-/-)和Igf-1(-/-)/Igf-2(-)双突变体中，侏儒症进一步加剧（正常大小的30%）。本文讨论了这些突变体之间表型差异所揭示的IGF在小鼠胚胎发育中的作用。
