Open AccessPten heterozygosity restores neuronal morphology in fragile X syndrome mice
Author(s) -
Shivaprasad H. Sathyanarayana,
Jasmine A Saunders,
Jacob Slaughter,
Kamran Tariq,
Rajarshi Chakrabarti,
Madhumala K. Sadanandappa,
Bryan W. Luikart,
Giovanni Bosco
Publication year - 2022
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2109448119
Subject(s) - pten , tensin , fmr1 , loss of heterozygosity , biology , phenotype , phosphatase , knockout mouse , fragile x syndrome , microbiology and biotechnology , genetics , pi3k/akt/mtor pathway , cancer research , fragile x , gene , signal transduction , phosphorylation , allele
Significance Phosphatase and tensin homolog protein (PTEN) and fragile X mental retardation protein (FMRP) play a vital role in neuronal development and function. This work provides new evidence for the genetic interaction ofPten andFmr1 in postnatal development of granule neurons and conserved mechanisms across evolution. The observed cellular phenotypic defects inPten andFmr1 knockout (KO) could be rectified and restored by heterozygosity ofPten inFmr1 KO neurons. Additionally, increased expression of PTEN in backgroundFmr1 KO animals suggests that FMRP negatively regulates PTEN, and we propose that introducing a combination of genetic mutations may normalize structural aspects of neuronal morphology by balancing each other’s expression.