Research Models

Bace1 conditional knock-out (neonatal, forebrain) (Vassar)

Synonyms: Bace1 cKO, BACE1fl/fl;CamKIIα-iCre

Species: Mouse
Genes: Bace1
Modification: Bace1: Conditional Knock-out
Disease Relevance: Alzheimer's Disease
Strain Name: N/A
Genetic Background: C57BL6
Availability: BACE1fl/fl available through Robert Vassar;  CamKIIα-iCre available through the European Mouse Mutant Archive (EMMA) ID# EM: 01153, cryopreserved, sperm

Summary

In these conditional knock-out mice, Bace1 expression is eliminated in forebrain excitatory neurons beginning during the first postnatal week. These mice were generated by crossing mice with a floxed Bace1 gene to mice carrying a transgene encoding Cre recombinase driven by the CamKIIα promoter (hereafter, these crosses are referred to as “BACE1-deficient mice”).

Unless stated otherwise, this description refers to comparisons between BACE1-deficient mice and mice homozygous for the floxed Bace1 gene that do not express Cre recombinase (hereafter “control”). Survival rates are similar in BACE1-deficient mice and control mice. While BACE1-deficient mice are smaller than controls at younger ages, body weights of the two genotypes are similar by 3 months. No gender differences are observed.

By four days of age BACE1 protein is no longer detectable in the forebrains of BACE1-deficient mice. Loss of BACE1 is accompanied by the accumulation of full-length BACE1 substrates (APP, CHL1, Sez6) and reduced levels of cleavage products BACE1 (cleaved CHL1, NRG1, Sez6, and APP β-CTF).

Hypomyelination and defects in axon organization were observed in BACE1-deficient mice, similar to what has been reported in mice with germline knock out of Bace1.

BACE1-deficient mice showed delayed learning, but normal memory, in the Morris water maze at 6 and 9 months of age. Alternation in the Y-maze test of working memory and cued- and contextual- fear conditioning were also normal. However, BACE1-deficient mice exhibited hyperactivity when placed in novel environments.

Spontaneous behavioral seizures and abnormal EEGs (epileptiform discharges) were seen in BACE1-deficient mice, although electrographic seizure activity is not as severe as in mice with germline knockout of Bace1.

Modification Details

Mice in which exon 2 of Bace1 is flanked by LoxP sites (BACE1fl/fl) were crossed with mice carrying a transgene encoding Cre recombinase driven by the CamKIIα promoter (Casanova et al., 2001).

 

Phenotype Characterization

When visualized, these models will distributed over a 18 month timeline demarcated at the following intervals: 1mo, 3mo, 6mo, 9mo, 12mo, 15mo, 18mo+.

Absent

No Data

  • Plaques
  • Tangles
  • Neuronal Loss
  • Gliosis
  • Synaptic Loss
  • Changes in LTP/LTD

Plaques

No data.

Tangles

No data.

Neuronal Loss

No data.

Gliosis

No data.

Synaptic Loss

No data.

Changes in LTP/LTD

No data.

Cognitive Impairment

Delayed learning, but normal memory, in the Morris water maze; normal alternation in the Y-maze test of working memory, normal cued and contextual fear conditioning.

Last Updated: 22 Feb 2019

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References

Paper Citations

  1. . A CamKIIalpha iCre BAC allows brain-specific gene inactivation. Genesis. 2001 Sep;31(1):37-42. PubMed.

Other Citations

  1. Robert Vassar

External Citations

  1. European Mouse Mutant Archive (EMMA) ID# EM: 01153

Further Reading