Research Models

APP Knock-out

Synonyms: APP null, APP KO

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Species: Mouse
Genes: APP
Modification: APP: Knock-Out
Disease Relevance: Alzheimer's Disease
Strain Name: B6.129S7-Apptm1Dbo/J
Genetic Background: C57BL/6J
Availability: The Jackson Lab: Stock# 004133; Live

Summary

The endogenous APP gene was disrupted in these animals by homologous recombination. At birth, mice homozygous for the targeted allele are viable and do not display any gross physical or behavioral abnormalities. No APP gene product (mRNA or protein) is detected. The body weight of both male and female homozygous animals is 15-20 percent less at all ages compared with that of wild-type, age-matched, mice. By 14 weeks, the mice exhibit elevated reactive gliosis in the hippocampus and neocortex compared to levels observed in wild-type animals. Neurological evaluation showed reduced forelimb grip strength and decreased locomotor activity (Zheng et al., 1995).

Modification Details

Inactivation of the mouse APP gene by replacing a 3.8 kb sequence encoding the promoter and exon 1 with a neomycin resistance cassette.

Last Updated: 09 Mar 2018

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References

Paper Citations

  1. Zheng H, Jiang M, Trumbauer ME, Sirinathsinghji DJ, Hopkins R, Smith DW, Heavens RP, Dawson GR, Boyce S, Conner MW, Stevens KA, Slunt HH, Sisoda SS, Chen HY, Van der Ploeg LH. beta-Amyloid precursor protein-deficient mice show reactive gliosis and decreased locomotor activity. Cell. 1995 May 19;81(4):525-31. PubMed.

External Citations

  1. The Jackson Lab: Stock# 004133

Further Reading

Papers

  1. Wang P, Yang G, Mosier DR, Chang P, Zaidi T, Gong YD, Zhao NM, Dominguez B, Lee KF, Gan WB, Zheng H. Defective neuromuscular synapses in mice lacking amyloid precursor protein (APP) and APP-Like protein 2. J Neurosci. 2005 Feb 2;25(5):1219-25. PubMed.
  2. Yang G, Gong YD, Gong K, Jiang WL, Kwon E, Wang P, Zheng H, Zhang XF, Gan WB, Zhao NM. Reduced synaptic vesicle density and active zone size in mice lacking amyloid precursor protein (APP) and APP-like protein 2. Neurosci Lett. 2005 Aug 12-19;384(1-2):66-71. PubMed.
  3. Degiorgio LA, Shimizu Y, Chun HS, Cho BP, Sugama S, Joh TH, Volpe BT. APP knockout attenuates microglial activation and enhances neuron survival in substantia nigra compacta after axotomy. Glia. 2002 Apr 15;38(2):174-8. PubMed.
  4. Degiorgio LA, Shimizu Y, Chun HS, Kim YS, Sugama S, Son JH, Joh TH, Volpe BT. Amyloid precursor protein gene disruption attenuates degeneration of substantia nigra compacta neurons following axotomy. Brain Res. 2002 May 31;938(1-2):38-44. PubMed.
  5. Dawson GR, Seabrook GR, Zheng H, Smith DW, Graham S, O'Dowd G, Bowery BJ, Boyce S, Trumbauer ME, Chen HY, van der Ploeg LH, Sirinathsinghji DJ. Age-related cognitive deficits, impaired long-term potentiation and reduction in synaptic marker density in mice lacking the beta-amyloid precursor protein. Neuroscience. 1999 Apr;90(1):1-13. PubMed.
  6. Seabrook GR, Smith DW, Bowery BJ, Easter A, Reynolds T, Fitzjohn SM, Morton RA, Zheng H, Dawson GR, Sirinathsinghji DJ, Davies CH, Collingridge GL, Hill RG. Mechanisms contributing to the deficits in hippocampal synaptic plasticity in mice lacking amyloid precursor protein. Neuropharmacology. 1999 Mar;38(3):349-59. PubMed.
  7. Zheng H, Jiang M, Trumbauer ME, Hopkins R, Sirinathsinghji DJ, Stevens KA, Conner MW, Slunt HH, Sisodia SS, Chen HY, van der Ploeg LH. Mice deficient for the amyloid precursor protein gene. Ann N Y Acad Sci. 1996 Jan 17;777:421-6. PubMed.