Creation of a laminin receptor I/ribosomal protein Sa deficient mouse

We have created a transgenic mouse heterozygous at the Laminin Receptor I (LAMR1) locus. LAMR1 encodes a multifunctional protein that is both an integral component of the 40S ribosomal subunit (ribosomal protein Sa) and a laminin receptor on the cell surface. Studies in yeast have shown that orthologs of LAMR1, RPS0A/B, are required for the maturation of 40S ribosomal subunits. As there are a growing number of human diseases linked to failures in ribosome synthesis, we were interested in the effect of a deficiency for LAMR1 on mouse development. Our data suggests haploinsufficiency for LAMR1 does not lead to embryonic lethality. Phenotypic analysis reveals that LAMR1 heterozygotes have a higher frequency of craniofacial abnormalities, reduction in red blood cell count, and higher incidence of premature deaths relative to their wild‐type littermates. To understand the molecular basis for these phenotypic characteristics, we have analyzed the effect of LAMR1 haploinsufficiency on the protein synthetic capacity of tissues and cells derived from the hemizygous mice. We were surprised to find that polysome profiles from the LAMR1 heterozygotes appeared more robust than those from wild‐type littermates. Moreover, embryo fibroblasts from the heterozygous mice grew at a faster rate than those derived from normal mice. These unexpected findings suggest that normal levels of LAMR1 may have a repressive effect on protein synthetic capacity in mice, and that changes associated with haploinsufficiency can impact normal mouse development. This work was supported by grants from the National Heart, Lung, and Blood Institute and Kentucky Lung Cancer Research Program