Activins are critical modulators of growth and survival.
Activins betaA and betaB (encoded by Inhba and Inhbb genes, respectively) are related members of the TGF-beta superfamily. Previously, we generated mice with an Inhba knock-in allele (InhbaBK) that directs the expression of activin betaB protein in the spatiotemporal pattern of activin betaA. These mice were small and had shortened life spans, both influenced by the dose of the hypomorphic InhbaBK allele. To understand the mechanism(s) underlying these abnormalities, we now examine growth plates, liver, and kidney and analyze IGF-I, GH, and major urinary proteins. Our studies show that activins modulate the biological effects of IGF-I without substantial effects on GH, and that activin signaling deficiency also has modest effects on hepatic and renal function. To assess the relative influences of activin betaA and activin betaB, we produced mice that express activin betaB from the InhbaBK allele, and not from its endogenous Inhbb locus. InhbaBK/BK, Inhbb-/- mice have failure of eyelid fusion at birth and demonstrate more severe effects on somatic growth and survival than either of the corresponding single homozygous mutants, showing that somatic growth and life span are supported by both activins betaA and betaB, although activin betaA plays a more substantial role.
Brown
Chester W
CW
Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA. cbrown@bcm.tmc.edu.
Li
Liunan
L
Houston-Hawkins
Dianne E
DE
Matzuk
Martin M
MM
D000818:Animals; D002455:Cell Division; D002470:Cell Survival; D005143:Eyelids / Q000196:embryology; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D013006:Growth Hormone / Q000097:blood; D006132:Growth Plate / Q000502:physiology*; D028322:Inhibin-beta Subunits / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007668:Kidney / Q000502:physiology; D008099:Liver / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011507:Proteinuria; D012260:Ribonucleases / Q000235:genetics
C103008:inhibin beta A subunit; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D028322:Inhibin-beta Subunits; D012260:Ribonucleases