Effects of Igf1 gene deletion on postnatal growth patterns.
This study documents the temporal and organ-specific effects of Igf1 gene deletion on postnatal growth patterns. Igf1-/- mice are 63+/-4% the size of wildtype (wt) littermates at birth and this ratio persists through postnatal day 20 (P20). After P20, Igf1-/- mice virtually stop growing, while wt littermates double in size from P20 to P40, after which their growth markedly decelerates. As a result, 'full-grown' Igf1-/- mice are less than one third the size of wt littermates. Igf1 gene deletion has disproportionate effects on organ growth. For example, at P10 and P40, Igf1-/- body weights are 63% and 31% of wt, respectively, while Igf1-/- lungs weigh only 34% and 22% of wt at these ages. In contrast, the Igf1-/- heart is disproportionately enlarged, representing approximately 85% of wt at P10 and approximately 56% at P40. Igf1-/- kidney, spleen and liver are slightly but significantly increased in size relative to the degree of reduction in Igf1-/- body weight. These data demonstrate that Igf1 has two major phases or modes of growth promotion. There is an early, growth hormone (GH)-independent Igf1 growth augmentation during perinatal development, responsible for about 35% of growth prior to P20. Then there are later effects due to GH-induced Igf1, which are responsible for increasing animal size by approximately 100% between P20 and 40. The fact that there is virtually no GH-induced growth in the Igf1-/- mice supports the view that Igf1 mediates GH's major effects on somatic growth. Finally, this study shows that Igf1 has discordant effects on pulmonary and cardiac growth parameters, with relative hypoplasia of Igf1-/- lungs and hypertrophy of Igf1-/- hearts.
Wang
J
J
Developmental Endocrinology Branch, NICHD, NIH, Bethesda, MD 20892, USA.
Zhou
J
J
Powell-Braxton
L
L
Bondy
C
C
D000375:Aging / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development*; D001835:Body Weight / Q000502:physiology; D017353:Gene Deletion; D006321:Heart / Q000033:anatomy & histology; D007334:Insulin-Like Growth Factor I / Q000235:genetics*; D007668:Kidney / Q000033:anatomy & histology; D008099:Liver / Q000033:anatomy & histology; D051379:Mice / Q000235:genetics; D009929:Organ Size / Q000502:physiology; D013154:Spleen / Q000033:anatomy & histology
D007334:Insulin-Like Growth Factor I