A Murine Model for Human Immune Thrombocytopenic Purpura and Comparative Analysis of Multiple Gene Expression in Bone Marrow and Spleen

J Genet Genomics. 2008 Nov;35(11):665-71. doi: 10.1016/S1673-8527(08)60088-0.

Abstract

Homeostasis of platelet number in human and other mammals is well maintained for prevention of minor bleeding and for other immunological functions, but the exact molecular mechanism responsible for immune thrombocytopenic purpura (ITP) has not been fully understood. In an effort to identify genetic factors involved in initiation of platelet production in response to bleeding injury or platelet destruction, we have successfully generated an animal model of human ITP via intraperitoneal injection of anti-platelet antibody into the Balb/c mouse. Platelet counts were dropped dramatically in animals that received antibody injection within 4 h, maintained at the minimum level for a period of 44 h, started to rebound after 48 h, and reached to the maximum at 144 h (6 days). Final homeostasis reached at approximately 408 h (17 days), following a minor cycle of platelet number fluctuation. Using semi-quantitative RT-PCR, we assessed and compared mRNA level of CD41, c-myb, c-mpl, caspase-3, caspase-9, GATA-1, and Bcl-xl in bone marrow and spleen. Alteration of mRNA expression was correlated with the change of platelet level, and an inverse relationship was found for expression of the genes between bone marrow and spleen. No transcription was detectable for any of the seven genes in bone marrow at the time when platelet number reached the maximum (144 h). In contrast, mRNA transcripts of the seven genes were found to be at the highest level in spleen tissue. This is the first study of simultaneous detection of multiple platelet related genes in a highly reproducible ITP animal model. Our results provided the supportive evidence that expression of the above seven genes are more related to negative regulation of platelet number in spleen tissue, at least in the model animals.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies / administration & dosage
  • Antibodies / immunology
  • Blood Platelets / immunology
  • Bone Marrow / metabolism*
  • Bone Marrow / pathology
  • Disease Models, Animal*
  • Female
  • Gene Expression Regulation*
  • Guinea Pigs
  • Humans
  • Male
  • Mice
  • Purpura, Thrombocytopenic / genetics*
  • Purpura, Thrombocytopenic / immunology*
  • Purpura, Thrombocytopenic / pathology
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Spleen / metabolism*
  • Time Factors

Substances

  • Antibodies
  • RNA, Messenger