Mice humanised for the EGF receptor display hypomorphic phenotypes in skin, bone and heart

Citations Over TimeTop 14% of 2003 papers

Abstract

Mice lacking the epidermal growth factor receptor (EGFR) develop epithelial defects and a neurodegenerative disease and die within the first month of birth. By employing a conditional knock-in approach using the human EGFR cDNA mice humanised for EGFR (hEGFRKI/KI) were generated. Homozygous hEGFRKI/KI mice are viable and live up to six months. However, these mice are growth retarded and show skin and hair defects similar to Egfr-/- mutants. Interestingly, the neurodegeneration is fully rescued in hEGFRKI/KI mice, however, they develop a severe heart hypertrophy with semilunar valve abnormalities. Moreover, hEGFRKI/KI mice display accelerated chondrocyte and osteoblast differentiation, a phenotype that is also present in Egfr-/- mice and has not been previously described. The severity of the phenotypes correlates with the expression levels of the hEGFRKI allele, which is not efficiently expressed in epithelial and bone cells, but is expressed at similar and even higher levels as the endogenous Egfr in brain and heart. These results demonstrate that mice humanised for EGFR display tissue-specific hypomorphic phenotypes and describe a novel function for EGFR in bone development.

Related Papers

• → EFFECT OF THE NEMATODE PHASMARHABDITIS HERMAPHRODITA ON YOUNGSTAGES OF THE PEST SLUG ARION LUSITANICUS(2002)40 cited
• → Cloning and Characterization of Rat BAT3 cDNA(1999)20 cited
• → Anthoxanthum Mosaic Virus(1970)6 cited
• → HLA-B-associated transcript 3 (Bat3)/Scythe is essential for p300-mediated acetylation of p53(2007)127 cited
• → Ecological and evolutionary importance of neighbors in the grass Anthoxanthum odoratum(1990)20 cited