Tracking the Cartoon mouse phenotype: Hemopexin domain-dependent regulation of MT1-MMP pericellular collagenolytic activity.

ABSTRACT: Following ENU mutagenesis, a phenodeviant line was generated, termed the "Cartoon mouse," that exhibits profound defects in growth and development. Cartoon mice harbor a single S466P point mutation in the MT1-MMP hemopexin domain, a 200-amino acid segment that is thought to play a critical role in regulating MT1-MMP collagenolytic activity. Herein, we demonstrate that the MT1-MMP_S466P mutation replicates the phenotypic status of Mt1-mmp-null animals as well as the functional characteristics of MT1-MMP^-/- cells. However, rather than a loss-of-function mutation acquired as a consequence of defects in MT1-MMP proteolytic activity, the S466P substitution generates a misfolded, temperature-sensitive mutant that is abnormally retained in the endoplasmic reticulum (ER

SUBMITTER: Sakr M 

PROVIDER: S-EPMC5971454 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature