MICE CARRYING NULL MUTATIONS OF THE GENES ENCODING INSULIN-LIKE GROWTH FACTOR-I (IGF-1) AND TYPE-1 IGF RECEPTOR (IGF1R)
MICE CARRYING NULL MUTATIONS OF THE GENES ENCODING INSULIN-LIKE GROWTH FACTOR-I (IGF-1) AND TYPE-1 IGF RECEPTOR (IGF1R)
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DOI：
10.1016/0092-8674(93)90679-k
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发表时间：
1993-10-08
期刊：
影响因子：
64.5
通讯作者：
EFSTRATIADIS, A
中科院分区：
文献类型：
--
作者：
LIU, JP;BAKER, J;EFSTRATIADIS, A
胰岛素样生长因子1基因（Igf - 1）靶向破坏的纯合子新生小鼠表现出的生长缺陷严重程度与先前在可存活的Igf - 2基因缺失突变体中观察到的相似（为正常出生体重的60%）。根据遗传背景的不同，一些Igf - 1（-/-）侏儒小鼠在出生后不久死亡，而其他的则存活并达到成年。相比之下，Igf1r基因缺失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（为正常大小的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也观察到偏离正常的情况。Igf - 1（-/-）/Igf1r（-/-）双突变体在表型上与Igf1r（-/-）单突变体没有差异，而在Igf - 2（-）/Igf1r（-/-）和Igf - 1（-/-）/Igf - 2（-）双突变体中，它们表型相同，侏儒症进一步加剧（为正常大小的30%）。本文讨论了从这些突变体之间的表型差异所揭示的胰岛素样生长因子在小鼠胚胎发育中的作用。
Newborn mice homozygous for a targeted disruption of insulin-like growth factor gene 1 (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.