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Effects of Igf1 Gene Deletion on Postnatal Growth Patterns

Developmental Endocrinology Branch (J.W., J.Z., C.B.), NICHD, NIH, Bethesda, Maryland 20892; Cardiovascular Research Department (L.P.-B.), Genentech Inc., San Francisco, California

Address all correspondence and requests for reprints to: Carolyn Bondy, M.D., NIH, 10 Center Drive, Building 10, Room 10N 262, Bethesda, Maryland 20892.

	Abstract

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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 85% of wt at P10 and 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 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.

Received March 4, 1999.

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