OBJECTIVE: The Ndl gene, which encodes a novel kelch family protein, is expressed ubiquitously in mouse tissues. In vitro studies suggest that Ndl protein, which binds to actin filaments, functions as a cytoskeletal stabilizer. In order to elucidate a physiological function of Ndl in vivo, we generated Nd1-deficient (Ndl-/-) mice. METHODS: We developed Nd1-/- mice by standard gene targeting technique. Cardiac function was studied in wild type and Nd1-/- mice. RESULTS: Nd1-/- mice were viable and no gross anatomical abnormality was observed after birth. When mouse embryonic fibroblasts were cultured in the presence of cytochalasin D or doxorubicin, the number of apoptotic cells in the Nd1-/- cell culture was larger that that in the wild-type cell culture. Furthermore, Nd1-/- mice were sensitive to doxorubicin-induced cardiotoxicity with increased numbers of cardiomyocytes apoptosis. CONCLUSIONS: Although Nd1 is dispensable for normal mice development, Nd1 plays a protective role in doxorubicin-induced cardiotoxic responses.
OBJECTIVE: The Ndl gene, which encodes a novel kelch family protein, is expressed ubiquitously in mouse tissues. In vitro studies suggest that Ndl protein, which binds to actin filaments, functions as a cytoskeletal stabilizer. In order to elucidate a physiological function of Ndl in vivo, we generated Nd1-deficient (Ndl-/-) mice. METHODS: We developed Nd1-/- mice by standard gene targeting technique. Cardiac function was studied in wild type and Nd1-/- mice. RESULTS:Nd1-/- mice were viable and no gross anatomical abnormality was observed after birth. When mouse embryonic fibroblasts were cultured in the presence of cytochalasin D or doxorubicin, the number of apoptotic cells in the Nd1-/- cell culture was larger that that in the wild-type cell culture. Furthermore, Nd1-/- mice were sensitive to doxorubicin-induced cardiotoxicity with increased numbers of cardiomyocytes apoptosis. CONCLUSIONS: Although Nd1 is dispensable for normal mice development, Nd1 plays a protective role in doxorubicin-induced cardiotoxic responses.
Authors: Daniel R Croft; Diane Crighton; Michael S Samuel; Filipe C Lourenco; June Munro; Jenifer Wood; Karim Bensaad; Karen H Vousden; Owen J Sansom; Kevin M Ryan; Michael F Olson Journal: Cell Res Date: 2010-11-16 Impact factor: 25.617