They have the striking feature of rapid recovery following spinal cord injury. T1KO mice have impaired bone development and a 10% smaller body size than wild-type (WT) mice. We previously produced T1 knockout mice (T1KO mice) and examined some functions of CS.

CSGalNAcT1 (T1) is a key enzyme in CS synthesis, because this enzyme catalyzes the first unique step in CS synthesis, apart from heparan sulfate synthesis. The first step is shared with another glycosaminoglycan, heparan sulfate thus, the first unique step in CS synthesis is GalNAc transfer to the linker. ĬS synthesis is sequentially performed by approximately 15 enzymes including glycosyltransferases and sulfotransferases in three steps: (I) tetrasaccharide linker synthesis attached to the core protein (II) disaccharide repeat synthesis for GalNAc ( N-acetylgalactosamine)-GlcUA (glucuronic acid) and (III) sulfation of these sugars. Recently, the function of PNNs in the regulation of synaptic plasticity and memory has been investigated, and PNN abnormalities in relation to human mental diseases have been reported. PNNs modulate synaptic functions, particularly GABAergic inhibitory input via parvalbumin (PV) (+) neuronal cells.

In the central nervous system, CSPG-enriched areas are called perineuronal nets (PNNs), which are specialized structures that surround synapses and are specifically recognized by Wisteria floribunda lectin (WFA). These CSPGs are mainly localized in the extracellular matrix. For synthesis of CS proteoglycans (CSPGs), CS is attached to core proteins, such as aggrecan (AGR), neurocan, phosphacan, and versican. These results suggest that T1 is important for plasticity, probably due to regulation of CS-dependent PNNs, and that T1KO is a good model for investigation of PNNs.Ĭhondroitin sulfate (CS) is one of the most abundant glycosaminoglycans, which are composed of long, repeated disaccharide chains. In T1KO, we observed abnormalities in several behavioral tests, including the open-field test, acoustic startle response, and social preference. The amount of CS in PNNs was also diminished in T1KO compared to wild-type mice, although the amount of a major CS proteoglycan core protein, aggrecan, was not changed. Biochemical analysis of T1KO revealed that loss of this enzyme reduced the amount of CS by approximately 50% in various brain regions. To investigate the importance of CS, we produced and precisely examined mice that were deficient in the CS synthesizing enzyme, CSGalNAcT1 (T1KO). In the brain, CS proteoglycans are highly concentrated in perineuronal nets (PNNs), which surround synapses and modulate their functions. Chondroitin sulfate (CS) is an important glycosaminoglycan and is mainly found in the extracellular matrix as CS proteoglycans.

Miyata 110 value