Skip to main content

Generation of human disease models by homologous recombination in human embryonic stem cells


Homologous recombination technique has been applied to murine embryonic stem cells improving significantly our knowledge on the functionality of several genes. Human disease models are very valuable tools for the study of the phenotype as well as potential therapy for genetic diseases.

The derivation of mutant mice using the technique of homologous recombination has been essential in the generation of models for human diseases. Despite the success of homologous recombination in mouse embryonic stem cells to study many human pathologies, the morphological, developmental and genetic differences between human and mice pose significant limitations for the use of these mutant animals as models for human disorders.

In many cases, the mouse phenotype differs from t hat observed in humans. Human embryonic stem cells are non-transformed cells with the capacities of self-renewal and pluripotency, allowing them to differentiate into a wide range of cell types. Via genetic manipulation, human ES cells can also be used to model human diseases to study the disorder's etiology and pathology.

This is especially important where the in vivo animal models have failed to fully recapitulate the phenotype in the human diseases. We propose to generate a model of dilated cardiomyopathy using hES cells by homologous recombination. A single base change mutation will be introduced in the LMNA gene, which encodes the lamin A and lamin C proteins, components of the inner nuclear lamina.

This mutation that results in the change of one aminoacid has been associated with a high percentage of sudden death (45%) in affected members of a family, even though all the affected individuals are heterozygous for the mutation. Defining how lamin mutations alter cardiac cell biology will ultimately increase our understanding of the pathophysiology of dilated cardiomyopathy.

Call for proposal

See other projects for this call


Plaza De Asua, 1
Sondika - Bizkaia