Global growth deficiencies in mice lacking the ribosomal protein HIP/RPL29.
Because of their deleterious effects on developing organisms, ribosomal protein (RP) mutations have been poorly described in mammals, and only a few heterozygous mutations have been shown to be viable. This observation is believed to be due to the fact that each RP is an essential component in the assembly of a functional stable ribosome. Here, we created gene targeted mutant mice lacking HIP/RPL29, an RP associated with translationally active ribosomes in eukaryotes. In contrast to other RP mutants, HIP/RPL29 null mice are viable but are up to 50% smaller than their control littermates at weaning age. In null embryos, delayed global growth is first observed around mid-gestation, and postnatal lethality due to low birth weight results in distortion of the Mendelian ratio. Prenatal growth defects are not fully compensated for during adulthood, and null animals display proportionately smaller organs and stature, and reach sexual maturity considerably later when compared with their control siblings. Additionally, HIP/RPL29 null embryonic fibroblasts have decreased rates of proliferation and protein synthesis and exhibit reduced steady state levels of core RPs. Altogether, our findings provide conclusive genetic evidence that HIP/RPL29 functions as an important regulator of global growth by modulating the rate of protein synthesis.
Kirn-Safran
Catherine B
CB
Department of Biological Sciences, University of Delaware, Newark, Delaware 19716, USA. ckirn@udel.edu
Oristian
Daniel S
DS
Focht
Richard J
RJ
Parker
Shaila G
SG
Vivian
Jay L
JL
Carson
Daniel D
DD
D000818:Animals; D015153:Blotting, Western; D049109:Cell Proliferation; D017931:DNA Primers; D004591:Electrophoresis, Polyacrylamide Gel; D047108:Embryonic Development / Q000235:genetics*; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D006128:Growth / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D008856:Microscopy, Fluorescence; D009154:Mutation / Q000235:genetics; D011132:Polyribosomes / Q000737:chemistry; D014176:Protein Biosynthesis / Q000235:genetics*; D016601:RNA-Binding Proteins; D012269:Ribosomal Proteins / Q000235:genetics*
D017931:DNA Primers; D016601:RNA-Binding Proteins; D012269:Ribosomal Proteins; C084343:Rpl29 protein, mouse