Research Models

Plcg2 KO

Synonyms: Plcg2 knock-out

Species: Mouse
Genes: Plcg2
Modification: Plcg2: Knock-Out
Disease Relevance: Alzheimer's Disease
Strain Name: B6(SJL)-Plcg2em2Adiuj/J
Genetic Background: C57BL/6J
Availability: Available Fall, 2018 from The Jackson Laboratory, Stock# 29910

Summary

Plcg2 (phospholipase C, gamma 2) is highly expressed in microglia, and a rare coding variant, rs72824905 (p.P522R), has been found to decrease AD risk by almost one-third (Sims, et al., 2017). Another rare variant, rs61749044 (p.M28L), was found to be associated with increased risk of AD in the Alzheimer’s Disease Sequencing Project cohort (M. Sasner, personal communication; presentation at 2018 AAIC). Heterozygous mutations within the PLCG2 gene cause PLCG2-associated antibody deficiency and immune dysregulation (PLAID).

CRISPR/Cas9 was used to introduce a knock-out mutation into the Plcg2 gene. Heterozygotes are viable and fertile, but homozygous viability/fertility has not yet been tested.

Modification Details

CRISPR/Cas9 was used to introduce a knock-out mutation into the Plcg2 gene of mice with a humanized APOE4 allele (B6(SJL)-Apoetm1.1(APOE*4)Adiuj/J, The Jackson Laboratory, Stock# 27894). These mice were then bred to C57BL/6J mice (The Jackson Laboratory, Stock# 000664) to breed out the humanized APOE4 allele.

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
  • Cognitive Impairment

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

No data.

Last Updated: 07 Jul 2018

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References

Paper Citations

  1. . Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease. Nat Genet. 2017 Sep;49(9):1373-1384. Epub 2017 Jul 17 PubMed.

External Citations

  1. PLCG2-associated antibody deficiency and immune dysregulation (PLAID)
  2. The Jackson Laboratory, Stock# 27894
  3. The Jackson Laboratory, Stock# 000664
  4. The Jackson Laboratory, Stock# 29910

Further Reading

No Available Further Reading