Targeted disruption of the low-affinity leukemia inhibitory factor receptor gene causes placental, skeletal, neural and metabolic defects and results in perinatal death.
The low-affinity receptor for leukemia inhibitory factor (LIFR) interacts with gp130 to induce an intracellular signal cascade. The LIFR-gp130 heterodimer is implicated in the function of diverse systems. Normal placentation is disrupted in LIFR mutant animals, which leads to poor intrauterine nutrition but allows fetuses to continue to term. Fetal bone volume is reduced greater than three-fold and the number of osteoclasts is increased six-fold, resulting in severe osteopenia of perinatal bone. Astrocyte numbers are reduced in the spinal cord and brain stem. Late gestation fetal livers contain relatively high stores of glycogen, indicating a metabolic disorder. Hematologic and primordial germ cell compartments appear normal. Pleiotropic defects in the mutant animals preclude survival beyond the day of birth.
Ware
C B
CB
Immunex, Seattle, WA 98101, USA.
Horowitz
M C
MC
Renshaw
B R
BR
Hunt
J S
JS
Liggitt
D
D
Koblar
S A
SA
Gliniak
B C
BC
McKenna
H J
HJ
Papayannopoulou
T
T
Thoma
B
B
D000818:Animals; D001253:Astrocytes / Q000166:cytology; D001483:Base Sequence; D015139:Blotting, Southern; D001846:Bone Development; D002452:Cell Count; D017931:DNA Primers / Q000235:genetics; D005314:Embryonic and Fetal Development; D005313:Fetal Death / Q000235:genetics; D017353:Gene Deletion; D006003:Glycogen / Q000378:metabolism; D006131:Growth Inhibitors; D006410:Hematopoiesis / Q000502:physiology; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit; D008099:Liver / Q000196:embryology / Q000378:metabolism; D008222:Lymphokines / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D009420:Nervous System / Q000196:embryology; D010010:Osteoclasts / Q000166:cytology; D010920:Placenta / Q000502:physiology; D016133:Polymerase Chain Reaction; D018121:Receptors, Cytokine / Q000235:genetics*; D053606:Receptors, OSM-LIF; D013234:Stem Cells / Q000502:physiology
D017931:DNA Primers; D006131:Growth Inhibitors; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit; C507838:Lif protein, mouse; C507841:Lifr protein, mouse; D008222:Lymphokines; D018121:Receptors, Cytokine; D053606:Receptors, OSM-LIF; D006003:Glycogen