Targeted disruption of the low-affinity leukemia inhibitory factor receptor gene causes placental, skeletal, neural and metabolic defects and results in perinatal death

Carol B. Ware, Mark C. Horowitz, Blair R. Renshaw, Joan S. Hunt, Denny Liggitt, Simon A. Koblar, Brian C. Gliniak, Hilary J. McKenna, Thalia Papayannopoulou, Bettina Thoma, Linzhao Cheng, Peter J. Donovan, Jacques J. Peschon, Perry F. Bartlett, Cynthia R. Willis, Barbara D. Wright, Melissa K. Carpenter, Barry L. Davison, David P. Gearing

Research output: Contribution to journalArticlepeer-review

506 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1283-1299
Number of pages17
JournalDevelopment
Volume121
Issue number5
StatePublished - May 1995
Externally publishedYes

Keywords

  • Astrocytes
  • Glycogen store
  • Mouse
  • Osteoporosis
  • Primordial germ cell

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology

Fingerprint

Dive into the research topics of 'Targeted disruption of the low-affinity leukemia inhibitory factor receptor gene causes placental, skeletal, neural and metabolic defects and results in perinatal death'. Together they form a unique fingerprint.

Cite this