Transgenic mice overexpressing TERT (TERT-tg mice) exhibit increased expression of NMDA receptor subunits and phosphorylation of alpha-CaMKII, ASD-like behavioral phenotypes, and lowered threshold against electrically induced seizures; behavioral abnormalities in TERT-tg mice could be reversed by the NMDA receptor antagonist memantine (Kim et al., 2015). In the same report, the authors state that TERT SNPs associated with ASD in a Korean family-based association analysis (although no p -values showing the significance of association of individual SNPs with ASD were provided); the GAA and AGC haplotypes for rs2736115/rs2736118/rs4975605 were shown to have p-values of 0.031 and 0.029, respectively. A novel possibly damaging de novo missense variant in TERT has observed in an ASD proband from the Autism Sequencing Consortium (De Rubeis et al., 2014).
Molecular Function
Telomerase is a ribonucleoprotein polymerase that maintains telomere ends by addition of the telomere repeat TTAGGG. The enzyme consists of a protein component with reverse transcriptase activity, encoded by this gene, and an RNA component which serves as a template for the telomere repeat. Telomerase expression plays a role in cellular senescence, as it is normally repressed in postnatal somatic cells resulting in progressive shortening of telomeres.
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Overexpression of Telomerase Reverse Transcriptase Induces Autism-like Excitatory Phenotypes in Mice.
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
Full length mTERT cDNA was cloned in the pCAGGS expression vector under the human cytomegalovirus immediate-early enhancer linked to the chicken beta-actin promoter. Transgenic mice were generated by microinjection of purified DNA into pronuclei of fertilized eggs of FVB/N mice.
Allele Type: Transgenic
Strain of Origin: Genetic Background: FVB/N
ES Cell Line: Mutant ES Cell Line: Model Source: 14960598
Spontaneous post synaptic event amplitude: excitatory currents1
Increased
Description: Spontaneous mepscs have increased amplitude in the medial prefrontal slices (layer 5) in tert transgenic mice compared to wt
Exp Paradigm: NA
Description: Tert-tg mice have no preference for stimulus mouse over object in the three chamber social approach test, unlike wt controls
Exp Paradigm: NA
Description: Tert-tg mice have impaired nest building with increased amount of nest building material left over compared to wt controls
Exp Paradigm: NA
Description: Tert-tg mice have no preference for stranger stimulus mouse over familiar stimulus mouse in the three chamber social approach test, unlike wt controls
Exp Paradigm: NA
Description: Tert-tg mice have decreased anxiety levels compared to wt as they travel larger distance in the center of the open field as well as spend more time in the open arms in the elevated plus maze
Exp Paradigm: Open field test
Description: Tert-tg mice have decreased anxiety levels compared to wt as they travel larger distance in the center of the open field as well as spend more time in the open arms in the elevated plus maze
Exp Paradigm: Elevated plus maze test
Description: Expression of several genes including nestin, pax6 and tbr2 is increased at earlier stages of embryonic development around e10-e12.5 in tert transgenic mice overexpressing tert
Exp Paradigm: Western blot: embryonic brains
Description: Expression of several genes including nestin, pax6 and tbr2 is increased at earlier stages of embryonic development around e10-e12.5 in tert transgenic mice overexpressing tert
Exp Paradigm: Immunohistochemistry
Description: Several proteins are found to be increased in levels in the synaptic terminal postsynaptic density protein complex, including psd-95vglut1, synaptophysin and alpha-camkii
Exp Paradigm: NA
