An investigation of tumour susceptibility in a modified ATM-/- mouse with no thymoma risk

Francis, Tegan Adeline (2015). An investigation of tumour susceptibility in a modified ATM-/- mouse with no thymoma risk. University of Birmingham. Ph.D.

Preview

Francis15PhD.pdf
PDF - Accepted Version
Download (17MB)

Abstract

Ataxia telangiectasia (A-T) is characterised by a predisposition to the development of a range of lymphoid tumours of both T and B cell origin. Currently, Atm-/- mice develop an aggressive thymic lymphoma and die by 13 weeks of age. In order to overcome this barrier to long lived mice and expand the range of lymphoid tumours driven by Atm loss, I crossed the Atm-/- mouse with the nude mouse (nu-/-).

The resulting Atm-/-nu-/- mice had a greater lifespan compared to the Atm-/- mice (median survival of 175 days versus 91 days). Of 17/69 Atm-/-nu-/- mice that developed a tumour sixteen were of B cell origin occurring in the spleen, liver, gut and axillary nodes. Histological examination of the B cell-derived tumours revealed that they were phenotypically heterogeneous. No tumours were observed in the control mice (Atm+/+nu-/- or Atm+/+nu+/-).

Fluorescence in situ hybridisation (FISH) revealed the presence of IgH translocations in 1/6 B cell lymphomas and 2/6 tumours had an additional copy of Myc. M-FISH revealed clonal abnormalities involving chromosomes 17 and/or 18 in 5/6 tumours analysed.

We conclude that in contrast to T cell lymphoma development in Atm-/- mice, which is associated with immune gene translocations and Myc amplification, the Atm-/-nu-/- model of A-T gives B cell lymphomas arising at different stages of B cell development and may be more representative of the types of B cell lymphoma in patients with A-T.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):