Protective role of Nd1 in doxorubicin-induced cardiotoxicity.
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.
Department of Developmental Genetics (H2), Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba City, Japan.
Lisa
L
Fujimura
Yuji
Y
Matsudo
Myengmo
M
Kang
Yasuyuki
Y
Takamori
Takeshi
T
Tokuhisa
Masahiko
M
Hatano
D000818:Animals; D017304:Annexin A5 / Q000032:analysis; D017209:Apoptosis; D015152:Blotting, Northern / Q000379:methods; D015139:Blotting, Southern / Q000379:methods; D015638:Cytochalasin D; D004317:Doxorubicin; D004452:Echocardiography; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D018345:Mice, Knockout; D032383:Myocytes, Cardiac / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology; D011506:Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*
D017304:Annexin A5; D047908:Intracellular Signaling Peptides and Proteins; C432129:Nd1 protein, mouse; D011506:Proteins; D015638:Cytochalasin D; D004317:Doxorubicin