@phdthesis{Merkel2011,
  author    = {Merkel, Carla Jennifer},
  title     = {Characterisation of Mena Promoter Activity and Protein Expression in Wild-type and Gene-trapped Mice},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-70414},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2011},
  abstract  = {Proteins of the Ena/VASP protein family are important regulators of actin and participate in cell-cell and cell-matrix adhesions. To date, the physiological importance of Ena/VASP proteins for integrity of the cardiovascular system has remained unclear. To study cardiovascular functions of Mena and VASP, we used an established VASP knockout mouse in combination with a novel gene-trap-based model to ablate Mena function. In the mutated Mena mouse, the endogenous Mena gene is disrupted by the insertion of a β-galactosidase construct and β-galactosidase expression is under the control of the endogenous Mena promoter. X-gal staining of mouse organs revealed Mena promoter activity in smooth muscle layers of vessels, intestines and bronchioles, but also in cells of the brain, in cardiomyocytes and in the respiratory epithelium of bronchioles. In wild-type mice, Western blotting revealed differing protein expression patterns of VASP and Mena. Mena expression was observed in almost every tissue, predominantly in heart, lung, stomach, large intestine, testis, brain and eye. Additionally, the neuronalspecific Mena isoform was expressed in brain, eye, and slightly in heart and stomach. VASP protein, in contrast, was predominantly detected in spleen and thrombocytes. In gene-trapped mice, Mena expression was largely reduced in heart, lung and stomach but only slightly decreased in brain and testis. Immunofluorescence microscopy revealed colocalisation of Mena and F-actin at intercalated discs of cardiomyocytes and strong colocalisation of Mena and α- smooth-muscle-actin in vessels and bronchioles. Functional analysis of Mena/VASP-mutated and wild-type mice using electrocardiography suggested that the depletion of either Mena or VASP does not interfere with normal heart function. However, in double-deficient mice, the resting heart rate was significantly increased, probably reflecting a mechanism to compensate defects in ventricle contraction and to maintain a normal cardiac output. In agreement, cardiac catheter investigations suggested dilated cardiomyopathy in doubledeficient mice. Thus, although Western blot analysis showed differing protein expression patterns of Mena and VASP, these findings suggest that Mena and VASP mutually compensate for each other. Concerning Mena, we propose an important role of the protein in vessel walls, cardiomyocytes and bronchioles.},
  subject      = {Spectrin},
  language  = {en}
}