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Generation of conditional null alleles for APP and APLP2
Jan-Philipp Mallm1, Jakob-Andreas Tschäpe, Meike Hick
1Department of Bioinformatics and Functional Genomics, Institute of Pharmacy and Molecular Biotechnology, University of Heidelberg, Heidelberg, Germany.
Genesis (New York, N.Y. : 2000)
|February 9, 2010
Summary
Researchers created new genetically modified mice to study the function of beta-amyloid precursor protein (APP) and APLP2. These mice enable precise control over gene deletion, aiding Alzheimer
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Beta-amyloid precursor protein (APP) cleavage produces beta-amyloid, a key component in Alzheimer's disease (AD) brain pathology.
- The physiological roles of APP and its homologues APLP1 and APLP2 are not fully understood.
- Previous studies showed APP and APLP2 are essential for survival, with double knockouts dying postnatally.
Purpose of the Study:
- To develop a tool for investigating the functions of APP and APLP2.
- To enable conditional, tissue-specific, and temporal deletion of APP and APLP2 genes.
- To overcome limitations of previous constitutive knockout models.
Main Methods:
- Generation of conditional knockout mouse lines for APP and APLP2 using loxP-flanked alleles.
- Crossing these conditional alleles with Cre-recombinase expressing transgenic mice.
- Verification of gene deletion efficiency and absence of phenotypic differences in floxed alleles compared to wild-type.
Main Results:
- Successfully generated conditional knockout alleles for both APP and APLP2.
- Confirmed that floxed alleles do not affect gene expression compared to wild-type.
- Established a method to achieve gene deletion upon Cre-mediated recombination.
Conclusions:
- Conditional knockout mice for APP and APLP2 are now available for research.
- These new models will facilitate the study of APP and APLP2 functions in a controlled manner.
- This advancement is crucial for understanding their roles in neurobiology and diseases like Alzheimer's.
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