Neonatal death in mice lacking cardiotrophin-like cytokine is associated with multifocal neuronal hypoplasia.
Mice with null mutations of ciliary neurotrophic factor (Cntf) receptor alpha (Cntf-Ralpha), or cytokine-like factor 1 (Clf), one component of Cntf-II (a heterodimeric Cntf-Ralpha ligand), die as neonates from motor neuron loss affecting the facial nucleus and ventral horn of the lumbar spinal cord. Exposure to cardiotrophin-like cytokine (Clc), the other putative Cntf-II element, supports motor neuron survival in vitro and in ovo. Confirmation that Clc ablation induces an equivalent phenotype to Clf deletion would support a role for Clc in the functional Cntf-II complex. In this study, Clc knockout mice had decreased facial motility, did not suckle, died within 24 hours, and had 32% and 29% fewer motor neurons in the facial nucleus and lumbar ventral horn, respectively; thus, Clc is essential for motor neuron survival during development. The concordance of the Clc knockout phenotype with those of mice lacking Cntf-Ralpha or Clf bolsters the hypothesis that Clc participates in Cntf-II.
Zou
X
X
Department of Inflammation Research, Amgen Inc., One Amgen Center Drive, MS 28-5-B, Thousand Oaks, CA 91320, USA. xzou@amgen.com
Bolon
B
B
Pretorius
J K
JK
Kurahara
C
C
McCabe
J
J
Christiansen
K A
KA
Sun
N
N
Duryea
D
D
Foreman
O
O
Senaldi
G
G
Itano
A A
AA
Siu
G
G
D000818:Animals; D000831:Animals, Newborn; D016207:Cytokines / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009046:Motor Neurons / Q000473:pathology; D018482:Muscle, Skeletal / Q000294:innervation; D013116:Spinal Cord / Q000473:pathology; D013118:Spinal Cord Diseases / Q000235:genetics* / Q000401:mortality
D016207:Cytokines; C121169:cardiotrophin-like cytokine