Screening of 9q33.1 copy number variants disrupting ASTN2 or both ASTN2 and TRIM32 in clinical microarray data from 89,986 individuals across 10 sites, including 64,114 subjects with neurodevelopmental disorders (NDD), in Lionel et al., 2014 found that deletions affecting both ASTN2 and TRIM32 were statistically enriched in NDD cases compared to controls (23 deletions in 64,114 cases vs. 6 in 44,085 controls; P-value 0.019); this enrichment was subsequently determined to be male-specific [22 deletions in 40,438 NDD males vs. 2 deletions in 14,953 male controls (P-value 0.024) compared to 1 deletion in 23.676 NDD females vs. 3 deletions in 18.218 female controls (P-value 0.964)]. Zhu et al., 2019 found that absence of TRIM32 resulted in impaired generation of GABAergic interneurons and autism-like behaviors in mice via suppressed mTOR signaling.
Molecular Function
The protein encoded by this gene is a member of the tripartite motif (TRIM) family and has an E3 ubiquitin ligase activity. The protein localizes to cytoplasmic bodies and has also been localized to the nucleus, where it interacts with the activation domain of the HIV-1 Tat protein.
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Absence of TRIM32 Leads to Reduced GABAergic Interneuron Generation and Autism-like Behaviors in Mice via Suppressing mTOR Signaling.
Rescue Type:
RESCUE-Pharmaceutical
Rescue Paradigm:
3BDO at 5-mg/kg/day was injected intraperitoneally into pregnant mice at E11.5 to E18.5 to achieve embryonic exposure and pups were tested at 1 month for immunofluorescence and 2 months for behavior. E11.5 to E18.5 is critical for interneuron generation.
Treatment does not improve measured phenotype (was expected to do so)
Ameliorated
Treatment provides partial correction or improvement of measured phenotype
No adverse effect
Treatment does not affect the parameter adversely
Sustained effect
Treatment has long term effect of restoration or amelioration, tested AFTER stopping administration (not applied for continuing long-term treatment) . Will be applied only where treatment has had restorative effects during administration or in the first battery of tests conducted.
No sustained effect
Treatment has no long term of restoration or amelioration detectable, after stopping administration. Will be applied only where treatment has had restorative effects during administration or in the first battery of tests conducted.
Description: 3bdo treatment increased time spent in the chamber with an unfamiliar mouse over time spent in the chamber with a familiar mouse.
Exp Paradigm: NA
Description: Quantification of cerebellar outline area showed that the cerebellar area of trim32â??/â?? mice was significantly smaller than area of wt mice Exp Paradigm: HandE staining sagittal sections
Dendritic architecture: dendritic tree complexity2
decreased
Description: Distal dendritic arborization of pcs was obviously decreased in trim32â??/â?? mice, as compared with wt mice although there was a slight increase in proximal dendritic arborization Exp Paradigm: Golgi-Cox staining
Description: Mild decrease in size of cerebella; no overt gross morphological alternations between mid-aged trim32â??/â?? and wt littermate cerebella Exp Paradigm: Macroscopic images
Description: Mutants show decrease in proliferation of neural precursor cells in the lge and mge. mutants show decrease in phosphohistone h3 positive cells in the mge at e13.5. mutants show decrease in nkx2.1 positive interneuron progenitors in the mge. Exp Paradigm: H3, nkx2.1
Description: Mutants show decreased numbers of brdu+gaba+ cells born at e13.5 in the hippocampus and the cortex at p18, and decreased numbers of gaba+ and glutamate decarboxylase 67 positive cells in the dentate gyrus at 3 weeks and 4 months. mutants show decrease in the numbers of interneuron subtypes including parvalbumin, calretinin, neuropeptide y, and somatostatin interneuron subtypes in the hippocampus at 3 weeks and 4 months. Exp Paradigm: Gaba, gad67, pv, clr, npy, sst
Description: Quantified the thickness of the cerebellar ml and found it was thinner in trim32â??/â?? cerebella compared with the cerebella in wt littermates Exp Paradigm: HandE staining sagittal sections
Anatomical projections and connectivity: purkinje cell-climbing fiber connections2
decreased
Description: Mean fluorescence intensity of vglut1-positive parallel fiber-purkinje cell connections and the number of vglut2-positive climbing fiber-purkinje cell connections were reduced in trim32â??/â?? mice
Description: Mutants show increase in the levels of microtubule-associated protein 1 light chain 3 (lc3)-ii, an indicator for formation of autophagosomes, in the embryonic mge. this increase of lc-ii is not blocked by chloroquine indicating the increase in lc-ii is not due to impaired autophagic influx. Exp Paradigm: NA
Description: Mutants show increased frequency of epileptic spikes in the hippocampus and cortex, indicating hyperexcitability and e/i imbalance. Exp Paradigm: NA
