Kent Lindsey N, Ohboshi Shigeki, Soares Michael J
Institute for Reproductive Health and Regenerative Medicine, Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, Kansas 66160, USA.
Int J Dev Biol. 2012;56(4):255-61. doi: 10.1387/ijdb.113407lk.
Phenotypic characterization of Akt1 and Igf2 null mice has revealed roles for each in the regulation of placentation, and fetal and postnatal growth. Insulin-like growth factor 2 (IGF2) is encoded by the Igf2 gene and influences cellular function, at least in part, through activation of an intracellular serine/threonine kinase called AKT1. Akt1 and Igf2 null mice were originally characterized on inbred and mixed genetic backgrounds, prohibiting direct comparisons of their phenotypes. The impact of loss of AKT1 or IGF2 on placental, fetal, and postnatal function were examined following transfer of Akt1 and Igf2 null mutations to an outbred CD1 genetic background. Disruption of IGF2 did not affect AKT expression or activation. Both Akt1-/- and Igf2-/- mice exhibited decreased placental weight, fetal weight and viability. Deregulation of placental growth was similar in Akt1 and Igf2 nulls; however, disruption of Igf2 had a more severe impact on prenatal survival and postnatal growth. Placental structure, including organization of junctional and labyrinth zones and development of the interstitial, invasive, trophoblast lineage, were similar in mutant and wild-type mice. Akt1 and Igf2 null mutations affected postnatal growth. The relative impact of each gene differed during pre-weaning versus post-weaning growth phases. AKT1 had a more significant role during pre-weaning growth, whereas IGF2 was a bigger contributor to post-weaning growth. Akt1 and Igf2 null mutations impact placental, fetal and postnatal growth. Placental phenotypes are similar; however, fetal and postnatal growth patterns are unique to each mutation.
Akt1基因敲除小鼠和Igf2基因敲除小鼠的表型特征揭示了它们在胎盘形成、胎儿及出生后生长调节中的作用。胰岛素样生长因子2（IGF2）由Igf2基因编码，至少部分通过激活一种名为AKT1的细胞内丝氨酸/苏氨酸激酶来影响细胞功能。最初对Akt1基因敲除小鼠和Igf2基因敲除小鼠的特征描述是基于近交和混合遗传背景，这使得无法直接比较它们的表型。在将Akt1和Igf2基因敲除突变转移到远交CD1遗传背景后，研究了AKT1或IGF2缺失对胎盘、胎儿及出生后功能的影响。IGF2的缺失不影响AKT的表达或激活。Akt1-/-和Igf2-/-小鼠均表现出胎盘重量、胎儿体重及活力下降。Akt1基因敲除小鼠和Igf2基因敲除小鼠的胎盘生长失调情况相似；然而，Igf2的缺失对产前存活和出生后生长的影响更为严重。突变小鼠和野生型小鼠的胎盘结构相似，包括连接区和迷路区的组织以及间质、侵袭性滋养层细胞系的发育。Akt1和Igf2基因敲除突变影响出生后生长。每个基因在断奶前和断奶后生长阶段的相对影响有所不同。AKT1在断奶前生长中起更重要的作用，而IGF2对断奶后生长的贡献更大。Akt1和Igf2基因敲除突变影响胎盘、胎儿及出生后生长。胎盘表型相似；然而，胎儿和出生后生长模式因每个突变而异。
