This project proposal aims to investigate the role of amyloid precursor protein (APP) in regulating male sexual behavior. The proposal involves using CRISPR interference to inactivate the APP gene specifically in excitatory neurons in the medial preoptic area of the brain. Live imaging will also be used to observe mRNA translocation in these neurons upon exposure to APP products. It is expected that CRISPRi inactivation of APP will reduce ejaculation behavior after castration and that iNOS mRNA will translocate upon exposure to amyloid-beta in medial preoptic area neurons.

1. EMS Snoeren et al. RS Oosting (2014) Pharmacol Biochem Behav
Amyloid precursor protein
regulation of male sexual behaviour
Project Proposal:
Vic Shao-Chih
Chiang, 2019

2. YC Wei et al. XH Xu (2018) Nat Commun
mPOA
Background

3. JH Park et al. EF Rissman (2010) J Neurosci
Background

4. • Heterogeneity of neuron subtypes in mPOA
• Gene inactivation of APP in mPOA excitatory
neurons on male sexual behavior
• Regulation of APP product on NO production
AIMS
Background

5. N Nitta et al. K Goda (2018) Cell
Intelligent image-activated cell
sorting for single-cell sequencing
Method

6. Y Zheng et al. J Yao (2019) Nat Neurosci
CRISPR Interference of APP
Method

7. JH Wu et al. SR Jaffrey (2019) Nat Methods
Live
imaging of
mRNA in
mPOA
neurons
Method

8. JR Moffitt et al. XW Zhuang (2018) Science
APP+ excitatory neurons in maters
Expected Outcome

9. CRISPRi inactivation of APP reduces
% ejaculation post-castration
Expected Outcome

10. iNOS mRNA
translocate in
exposure to Aβ
in mPOA
neurons
Modified from JH Wu et al. SR Jaffrey (2019) Nat Methods
Expected Outcome

11. L Chen et al. GJ Shi (2019) Biomed Pharmacother
Closing

12. Supplementary
N Nitta et al. K Goda (2018) Cell

13. Supplementary
OB Poirion et al. L Garmire (2016) Front Genet

14. Supplementary
A Lafzi et al. H Heyn (2018) Nat Protoc

15. Supplementary
JH Wu et al. SR Jaffrey (2019) Nat Methods

16. Supplementary
RG Will, EM Hull, JM Dominguez (2014) Pharmacol Biochem Behav