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Normal brain development in importin-5 deficient-mice
Tatjana Shmidt1, Franziska Hampich1, Michael Ridders1,2, Stefanie Schultrich1,2, Volkmar H. Hans3, Katja Tenner1, Larissa Vilianovich1, Fatimunnisa Qadri1, Natalia Alenina1, Enno Hartmann2, Matthias Khler4 and Michael Bader1
To the Editor:
Importins are essential components of the machinery that transports proteins into the nucleus of eukaryotic cells1,2. At present, six isoforms of -importins have been described in humans and five in mice. It has been shown that these isoforms exhibit overlapping as well as distinct cargo specificities3. A recent report in this journal has suggested that specific importin isoforms may be responsible for the nuclear import of transcription factors that are essential for differentiation processes and that a switch in isoforms during ontogenesis may be crucial for cell fate specification4. This study showed that mouse embryonic stem cells need to abrogate the expression of importin-1 and to activate the expression of importin-5 (karyopherin1) in order to undergo neuronal differentiation in vitro. A correspondingly high expression of importin-5 in the adult mouse brain and the absence of importin-1 in this tissue indicated that the in vitro findings may be relevant for the in vivo situation4,5. We set out to assess this issue by generating importin-5 knockout (Imp5/)
mice. On the basis of the study by Yasuhara et al.4, we would have expected severe abnormalities in neuronal differentiation and brain development. However, Imp5/ mice were born in normal mendelian ratios, were viable and fertile, and did not show any obvious morphological or behavioural abnormalities. These animals
did not express importin-5 in any of the tissues tested, including the brain, as assessed by RNase protection assay and western blot using specific probes and antibodies, respectively (Figs 1a, b). Thorough macroscopic and histopathologic analyses revealed orderly and indistinguishably developed brain and spinal cord in all animals investigated. As importin-5 mRNA has been found in adult mouse brain and cerebellum5 and importin-5 protein has been located in cerebellar Purkinje cells and hippocampal pyramidal cells6, we were particularly interested in these
structures. However, as shown for other areas of the central nervous system, neither cyto-architectural nor cytological abnormalities were evident, nor was there any conspicuous difference in cellularity in these structures (Fig....