TY  - JOUR
A1  - Rivero, Olga
A1  - Alhama-Riba, Judit
A1  - Ku, Hsing-Ping
A1  - Fischer, Matthias
A1  - Ortega, Gabriela
A1  - Álmos, Péter
A1  - Diouf, David
A1  - van den Hove, Daniel
A1  - Lesch, Klaus-Peter
T1  - Haploinsufficiency of the Attention-Deficit/Hyperactivity Disorder Risk Gene St3gal3 in Mice Causes Alterations in Cognition and Expression of Genes Involved in Myelination and Sialylation
T2  - Frontiers in Genetics
N2  - Genome wide association meta-analysis identified ST3GAL3, a gene encoding the beta-galactosidase-alpha-2,3-sialyltransferase-III, as a risk gene for attention-deficit/hyperactivity disorder (ADHD). Although loss-of-function mutations in ST3GAL3 are implicated in non-syndromic autosomal recessive intellectual disability (NSARID) and West syndrome, the impact of ST3GAL3 haploinsufficiency on brain function and the pathophysiology of neurodevelopmental disorders (NDDs), such as ADHD, is unknown. Since St3gal3 null mutant mice display severe developmental delay and neurological deficits, we investigated the effects of partial inactivation of St3gal3 in heterozygous (HET) knockout (St3gal3±) mice on behavior as well as expression of markers linked to myelination processes and sialylation pathways. Our results reveal that male St3gal3 HET mice display cognitive deficits, while female HET animals show increased activity, as well as increased cognitive control, compared to their wildtype littermates. In addition, we observed subtle alterations in the expression of several markers implicated in oligodendrogenesis, myelin formation, and protein sialylation as well as cell adhesion/synaptic target glycoproteins of ST3GAL3 in a brain region- and/or sex-specific manner. Taken together, our findings indicate that haploinsufficiency of ST3GAL3 results in a sex-dependent alteration of cognition, behavior and markers of brain plasticity.
KW  - sialyltransferase
KW  - sialic acid
KW  - psychiatric disorders
KW  - attention-deficit/hyperactivity disorder (ADHD)
KW  - prefrontal cortex
KW  - hippocampus
KW  - mouse model
Y1  - 2021
UR  - https://opus.bibliothek.uni-wuerzburg.de/frontdoor/index/index/docId/24685
UR  - https://nbn-resolving.org/urn:nbn:de:bvb:20-opus-246855
SN  - 1664-8021
VL  - 12
ER  -