Question

How does a transgeneic mouse model overexpress LMO2? Explain the process.

Answer 1

One of the causes of T-cell acute lymphoblastic leukemia (T-ALL) development is Overexpression of LMO2.

It is suggested in LMO2-overexpressing transgenic mouse models that accumulation of immature T-cell progenitors occurs in the thymus. Additionally, Lmo2 is not required for T-cell or B-cell development. The Lmo2 protein has two Zinc-coordinating LIM domains that are responsible for protein-protein interactions. Interestingly, the knockout mice for these factors have remarkably similar phenotypes, affecting primitive and adult hematopoiesis. Thus, Lmo2 and its associated macromolecular complex are critical for the specification of primitive and adult hematopoietic stem cells.

The effects of LMO2 overexpression were confined to the T-cell lineage; however, initially, multipotent cells were transduced.

Three effects of LMO2 on T-cell development were observed:

(1) a block at the double-negative/immature single-positive stage,

(2) an accumulation of CD4(+)CD8(+) double-positive CD3(-) cells, and

(3) an altered CD8/CD4 ratio with enhanced peripheral T lymphocytes. Microarray analysis of sorted double-positive cells overexpressing LMO2 led to the identification of an LMO2 gene set that clustered with human T-ALL patient samples of the described "proliferative" cluster.

Lmo2 is the best-characterized member that has been extensively studied in mouse models where it is a master regulator of hematopoiesis.

Additionally, Lmo2 is not required for T-cell or B-cell development. The Lmo2 protein has two Zinc-coordinating LIM domains that are responsible for protein-protein interactions. The knockout mice for these factors have remarkably similar phenotypes, affecting primitive and adult hematopoiesis. Thus, Lmo2 and its associated macromolecular complex are critical for the specification of primitive and adult hematopoietic stem cells.