Generation and Characterization of an EFHD2 Knockout Mice
Rodríguez Cruz, Eva Nilda
Vega, Irving E. (Consejero)
The calcium binding protein EF-hand domain 2 (EFHD2) is a novel amyloid protein associated with pathological forms of Tau in human Alzheimer's disease. Structural analyses revealed that EFHD2 contain two functional EF-hand domains, a Proline-rich region at the N-terminus and a coiled-coil domain at the C-terminus. The coiled-coil domain of EFHD2 mediates the formation of EFHD2' self-seeded filamentous structures and the EFHD2 –Tau association. Recent studies suggest that EFHD2 is involved in calcium influx, apoptosis, and regulation of actin filament bundling. Although Efhd2 gene is highly conserved, the physiological function of the protein is unknown. An Efhd2 knockout (Efhd2-/-) mouse was developed to understand the physiological role of EFHD2 in the central nervous system. Deletion of the Efhd2 gene did not affect embryonic or postnatal development. Efhd2-/- mice are viable and healthy, and have a tendency to a longer life span and lower body mass and lower levels of abdominal fat as compared to wild-type animals when compared to wild-type animals. Deletion of Efhd2 gene does not elicit impairments in motor function including, locomotion, neuromuscular function, coordination and balance or gait. Examination of cognitive function reveals that the deletion of Efhd2 does not impair spatial learning and memory of mice. The possibility of a compensation mechanism by one or multiple genes was examined. Abundance of the EFHD2 homologous protein, EFHD1, was not altered in adult Efhd2 knockout mice brains. Preliminary examination of gene expression profiles showed differential expression of 143 genes (92 up-regulated and 51 down-regulated) in Efhd2-/- mice at 10-weeks of age. In aged animals (80-weeks of age), a total of 230 genes are potentially deregulated (136 up-regulated and 94 down-regulated). Among the identified deferentially expressed transcripts include are transcripts coding for transcription factors, cytoskeletal proteins, immune system, calcium binding, hormones and peptides. Altogether, the development of the Efhd2-/- mice provides a novel research tool for the study of the biological function of EFHD2 and its role in aging and neurodegeneration.