Murine models of chronic lymphocytic leukaemia: role of microRNA-16 in the New Zealand Black mouse model

Br J Haematol. 2007 Dec;139(5):645-57. doi: 10.1111/j.1365-2141.2007.06851.x. Epub 2007 Oct 17.


Mouse models are valuable tools in the study of human chronic lymphocytic leukaemia (CLL). The New Zealand Black (NZB) strain is a naturally occurring model of late-onset CLL characterized by B-cell hyperproliferation and autoimmunity early in life, followed by progression to CLL. Other genetically engineered models of CLL that have been developed include (NZB x NZW) F1 mice engineered to express IL5, mice expressing human TCL1A, and mice overexpressing both BCL2 and a tumour necrosis factor receptor-associated factor. The applicability to human CLL varies with each model, suggesting that CLL is a multifactorial disease. Our work with the de novo NZB model has revealed many similarities to the human situation, particularly familial CLL. In NZB, the malignant clones express CD5, zap-70, and have chromosomal instability and germline Ig sequence. We also identified a point mutation in the 3'-flanking sequence of Mirn16-1, which resulted in decreased levels of the microRNA, miR-16 in lymphoid tissue. Exogenous restoration of miR-16 to an NZB malignant B-1 cell line resulted in cell cycle alterations, suggesting that the altered expression of Mirn15a/16-1 is an important molecular lesion in CLL. Future studies utilizing the NZB mouse could ascertain the role of environmental triggers, such as low dose radiation and organic chemicals in the augmentation of a pre-existing propensity to develop CLL.

Publication types

  • Review

MeSH terms

  • Animals
  • Base Sequence
  • Disease Models, Animal*
  • Leukemia, Lymphocytic, Chronic, B-Cell / genetics*
  • Mice
  • Mice, Inbred NZB
  • Mice, Transgenic
  • MicroRNAs / genetics*
  • Molecular Sequence Data
  • Point Mutation
  • RNA, Neoplasm / genetics*


  • MicroRNAs
  • RNA, Neoplasm