Mice with Combined Gene Knock-Outs Reveal Essential and Partially Redundant Functions of Amyloid Precursor Protein Family Members
10.1523/jneurosci.20-21-07951.2000
Crossref journal-article
Society for Neuroscience
The Journal of Neuroscience (393)
Abstract

The amyloid precursor protein (APP) involved in Alzheimer's disease is a member of a larger gene family including amyloid precursor-like proteins APLP1 and APLP2. We generated and examined the phenotypes of mice lacking individual or all possible combinations of APP family members to assess potential functional redundancies within the gene family. Mice deficient for the nervous system-specific APLP1 protein showed a postnatal growth deficit as the only obvious abnormality. In contrast to this minor phenotype, APLP2−/−/APLP1−/−and APLP2−/−/APP−/−mice proved lethal early postnatally. Surprisingly, APLP1−/−/APP−/−mice were viable, apparently normal, and showed no compensatory upregulation of APLP2 expression. These data indicate redundancy between APLP2 and both other family members and corroborate a key physiological role for APLP2. This view gains further support by the observation that APLP1−/−/APP−/−/APLP2+/−mice display postnatal lethality. In addition, they provide genetic evidence for at least some distinct physiological roles of APP and APLP2 by demonstrating that combinations of single knock-outs with the APLP1 mutation resulted in double mutants of clearly different phenotypes, being either lethal, or viable. None of the lethal double mutants displayed, however, obvious histopathological abnormalities in the brain or any other organ examined. Moreover, cortical neurons from single or combined mutant mice showed unaltered survival rates under basal culture conditions and unaltered susceptibility to glutamate excitotoxicityin vitro.

Bibliography

Heber, S., Herms, J., Gajic, V., Hainfellner, J., Aguzzi, A., Rülicke, T., Kretzschmar, H., von Koch, C., Sisodia, S., Tremml, P., Lipp, H.-P., Wolfer, D. P., & Müller, U. (2000). Mice with Combined Gene Knock-Outs Reveal Essential and Partially Redundant Functions of Amyloid Precursor Protein Family Members. The Journal of Neuroscience, 20(21), 7951–7963.

Authors 13
  1. Sabine Heber (first)
  2. Jochen Herms (additional)
  3. Vladan Gajic (additional)
  4. Johannes Hainfellner (additional)
  5. Adriano Aguzzi (additional)
  6. Thomas Rülicke (additional)
  7. Hans Kretzschmar (additional)
  8. Cornelia von Koch (additional)
  9. Sangram Sisodia (additional)
  10. Phillippe Tremml (additional)
  11. Hans-Peter Lipp (additional)
  12. David P. Wolfer (additional)
  13. Ulrike Müller (additional)
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Dates
Type When
Created 7 years, 4 months ago (April 5, 2018, 11:10 a.m.)
Deposited 2 years, 4 months ago (April 13, 2023, 9:39 a.m.)
Indexed 3 days, 21 hours ago (Aug. 24, 2025, 6:54 p.m.)
Issued 24 years, 9 months ago (Nov. 1, 2000)
Published 24 years, 9 months ago (Nov. 1, 2000)
Published Online 24 years, 9 months ago (Nov. 1, 2000)
Published Print 24 years, 9 months ago (Nov. 1, 2000)
Funders 0

None

@article{Heber_2000, title={Mice with Combined Gene Knock-Outs Reveal Essential and Partially Redundant Functions of Amyloid Precursor Protein Family Members}, volume={20}, ISSN={1529-2401}, url={http://dx.doi.org/10.1523/jneurosci.20-21-07951.2000}, DOI={10.1523/jneurosci.20-21-07951.2000}, number={21}, journal={The Journal of Neuroscience}, publisher={Society for Neuroscience}, author={Heber, Sabine and Herms, Jochen and Gajic, Vladan and Hainfellner, Johannes and Aguzzi, Adriano and Rülicke, Thomas and Kretzschmar, Hans and von Koch, Cornelia and Sisodia, Sangram and Tremml, Phillippe and Lipp, Hans-Peter and Wolfer, David P. and Müller, Ulrike}, year={2000}, month=nov, pages={7951–7963} }