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Mice bearing a targeted mutation of nBmp2 display decreased memory capabilities
Author(s) -
Dhungel Saroj,
Rogers Aubrey C,
Cordner Ryan D,
Mayo Jaime L,
Steed Kevin,
Badgley Corinne,
Wallmann Andrew,
Barrow Jeffrey R,
Edwards Jeffrey G,
Bridgewater Laura C
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.lb142
Subject(s) - mutant , microbiology and biotechnology , long term potentiation , mutation , calcium in biology , biology , nucleus , phenotype , hippocampal formation , calcium , neuroscience , chemistry , intracellular , genetics , gene , receptor , organic chemistry
A variant of the secreted growth factor BMP‐2, called nBmp2, is translated from a downstream alternative start codon and localized to the nucleus. To determine the function of this novel nuclear variant, we generated mice bearing a mutation that prevents nuclear localization of nBmp2 without altering production of secreted BMP‐2. Skeletal analysis of mutant compared to wild type mice demonstrated that skeletal structure is entirely normal in the mutant mice, indicating that the function of secreted BMP‐2 was not altered by the mutation and that any phenotypic differences, therefore, are due to exclusion of nBmp2 from the nucleus. Intracellular calcium handling is aberrant in muscle from these mice, so this study was undertaken to measure calcium‐dependent neurological function. Mutant mice displayed significantly impaired memory capabilities in both the Morris water maze and the novel object recognition test. Synaptic plasticity, which is dependent on calcium transport and is the main cellular mechanism mediating learning and memory, was tested by measuring long‐term potentiation in hippocampal slices and was found to be significantly reduced in the mutant mice. Our data suggest that nBmp2 plays an important role in the processes of memory and learning, perhaps by affecting calcium transport in neural tissue.