Generation of APLP2 KO mice and early postnatal lethality in APLP2/APP double KO mice

C. S. Von Koch, H. Zheng, H. Chen, M. Trumbauer, G. Thinakaran, L. H.T. Van Der Ploeg, D. L. Price, S. S. Sisodia

Research output: Contribution to journalArticle

Abstract

Amyloid precursor protein (APP) is a member of a larger gene family including amyloid precursor-like proteins (APLP), APLP2 and APLP1. To examine the function of APLP2 in vivo, we generated APLP2 knockout (KO) mice. They are of normal size, fertile, and appear healthy up to 22 months of age. We observed no impaired axonal outgrowth of olfactory sensory neurons following bulbectomy, suggesting against an important role for APLP2 alone in this process. Because APLP2 and APP are highly homologous and may serve similar functions in vivo, we generated mice with targeted APLP2 and APP alleles. Approximately 80% of double KO mice die within the first week after birth, suggesting that APLP2 and APP are required for early postnatal development. The surviving ~20% of double KO mice are 20-30% reduced in weight and show difficulty in righting, ataxia, spinning behavior, and a head tilt, suggesting a deficit in balance and/or strength. Adult double KO mice mate poorly, despite apparent normal ovarian and testicular development. Otherwise, double KO mice appear healthy up to 13 months of age. We conclude, that APLP2 and APP can substitute for each other functionally.

Original languageEnglish (US)
Pages (from-to)661-669
Number of pages9
JournalNeurobiology of Aging
Volume18
Issue number6
DOIs
StatePublished - Nov 1 1997

Keywords

  • Amyloid precursor protein
  • Amyloid precursor-like protein
  • Axonal outgrowth
  • Epithelium
  • Gene targeting
  • Olfactory

ASJC Scopus subject areas

  • Neuroscience(all)
  • Aging
  • Clinical Neurology
  • Developmental Biology
  • Geriatrics and Gerontology

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    Von Koch, C. S., Zheng, H., Chen, H., Trumbauer, M., Thinakaran, G., Van Der Ploeg, L. H. T., Price, D. L., & Sisodia, S. S. (1997). Generation of APLP2 KO mice and early postnatal lethality in APLP2/APP double KO mice. Neurobiology of Aging, 18(6), 661-669. https://doi.org/10.1016/S0197-4580(97)00151-6