Germline ablation of dermatan-4O-sulfotransferase1 reduces regeneration after mouse spinal cord injury

Rost, Sandra; Akyüz, Nuray; Martinović, Tamara; Huckhagel, Torge; Jakovčevski, Igor; Schachner, Melitta

doi:10.1016/j.neuroscience.2015.11.013

Cited by 14 publications

(7 citation statements)

References 54 publications

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“…Our group has shown that germline ablation of Chst-14 in mice reduces regeneration after SCI (21), whereas in the present study, Chst-14 knockdown in zebrafish did not alter innate regeneration. We cannot explain this phenomenon because expression of CS/DS-modifying enzymes during zebrafish embryonic development and in the adult has not been studied systematically.…”

Section: Discussioncontrasting

confidence: 85%

“…We generated a mouse mutant deficient in one of the enzymes transferring sulfate onto chondroitin (C4ST1/ Chst-11) (20) and another mutant deficient in the sulfotransferase adding sulfate to dermatan (D4ST1/Chst-14) (20)(21)(22). The phenotypes of these mutants in regeneration after nervous system injury were difficult to interpret in the sense that the regenerative capacity of the Chst-14deficient mutant was different between the central and peripheral nervous systems.…”

mentioning

confidence: 99%

“…The phenotypes of these mutants in regeneration after nervous system injury were difficult to interpret in the sense that the regenerative capacity of the Chst-14deficient mutant was different between the central and peripheral nervous systems. In the peripheral nervous system, this mutant was more efficient in regeneration of the severed femoral nerve, whereas, in the CNS after spinal cord injury (SCI), the mutant was less efficient in regeneration than the wild-type littermates (21,22). Furthermore, recessive loss-of-function mutations in Chst-14 in humans are characterized by multiple congenital malformations (e.g., craniofacial features including large fontanelles, hypertelorism, as well as short and downslanting palpebral fissures) and progressive multisystem fragilityrelated complications (e.g., skin hyperextensibility, bruisability that have been reported to cause a new type of Ehlers-Danlos syndrome (23).…”

mentioning

confidence: 99%

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Knockdown of chondroitin‐4‐sulfotransferase‐1, but not of dermatan‐4‐sulfotransferase‐1, accelerates regeneration of zebrafish after spinal cord injury

Sahu

Loers

et al. 2018

FASEB j.

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Glycosaminoglycans such as chondroitin sulfate (CS) and dermatan sulfate (DS) are long chains of repeating disaccharide units, covalently linked to core proteins to form proteoglycans. Proteoglycans can be cell membrane‐bound or are part of the extracellular matrix. They are important in a wide range of biologic processes, including development, synaptic plasticity, and regeneration after injury, as well as modulation of growth factor signaling, cell migration, survival, and proliferation. Synthesis of CS and DS in the Golgi apparatus is mediated by sulfotransferases that modify sugar chains through transfer of sulfate groups to specific positions on the sugar moieties. To clarify the functions of CS and DS during nervous system regeneration, we studied the effect of chondroitin 4‐O‐sulfotransferase‐1/carbohydrate sulfotransferase‐11 (C4ST‐l/Chst‐11) and dermatan 4‐O‐sulfotransferase‐1/Chst‐14 (D4ST‐l/Chst‐14) down‐regulation on spinal cord regeneration in larval and adult zebrafish. In our study, knockdown of C4ST1/Chst‐11 accelerated regeneration after spinal cord injury in larval and adult zebrafish and knockdown of D4ST1/Chst‐14 did not alter regenerative capacity. From these and previous observations, we drew the conclusion that different CS and DS expression patterns can be growth permitting, growth inhibiting, or neutral for regrowing or sprouting axons, depending on the tissue environment of a particular animal species.—Sahu, S., Li, R., Loers, G., Schachner, M. Knockdown of chondroitin‐4‐sulfotransferase‐l, but not of dermatan‐4‐sulfotransferase‐l, accelerates regeneration of zebrafish after spinal cord injury. FASEB J. 33, 2252–2262 (2019). http://www.fasebj.org

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Section: Discussioncontrasting

confidence: 85%

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confidence: 99%

mentioning

confidence: 99%

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Knockdown of chondroitin‐4‐sulfotransferase‐1, but not of dermatan‐4‐sulfotransferase‐1, accelerates regeneration of zebrafish after spinal cord injury

Sahu

Loers

et al. 2018

FASEB j.

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“…This was done using linear regression and comparing the density of cholinergic synapses with the “gold standard” BMS score (Basso et al, 2006 ), as well as the single-frame motion analysis locomotor scoring (Apostolova et al, 2006 ). Several other studies in the mouse model of spinal cord injury have consistently reported that the higher number of cholinergic synapses around motoneurons corresponds to the improved locomotor outcome (Cui et al, 2011 ; Xu et al, 2011 ; Lee et al, 2012 ; Wu et al, 2012 ; Papastefanaki et al, 2015 ; Rost et al, 2016 ; Saini et al, 2016 ). We additionally quantified VGAT-positive inhibitory synapses around motoneuron cell bodies, as well as glutamatergic synapses, but the changes among those were not consistent and are difficult to explain in terms of possible connections with functional recovery (Jakovcevski et al, 2007 ).…”

Section: Spinal Cord Injurymentioning

confidence: 94%

Confocal Synaptology: Synaptic Rearrangements in Neurodegenerative Disorders and upon Nervous System Injury

2018

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The nervous system is a notable exception to the rule that the cell is the structural and functional unit of tissue systems and organs. The functional unit of the nervous system is the synapse, the contact between two nerve cells. As such, synapses are the foci of investigations of nervous system organization and function, as well as a potential readout for the progression of various disorders of the nervous system. In the past decade the development of antibodies specific to presynaptic terminals has enabled us to assess, at the optical, laser scanning microscopy level, these subcellular structures, and has provided a simple method for the quantification of various synapses. Indeed, excitatory (glutamatergic) and inhibitory synapses can be visualized using antibodies against the respective vesicular transporters, and choline-acetyl transferase (ChAT) immunoreactivity identifies cholinergic synapses throughout the central nervous system. Here we review the results of several studies in which these methods were used to estimate synaptic numbers as the structural equivalent of functional outcome measures in spinal cord and femoral nerve injuries, as well as in genetic mouse models of neurodegeneration, including Alzheimer’s disease (AD). The results implicate disease- and brain region-specific changes in specific types of synapses, which correlate well with the degree of functional deficit caused by the disease process. Additionally, results are reproducible between various studies and experimental paradigms, supporting the reliability of the method. To conclude, this quantitative approach enables fast and reliable estimation of the degree of the progression of neurodegenerative changes and can be used as a parameter of recovery in experimental models.

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“…Pathophysiological mechanisms and therapies are not yet established for the disease. Several reports show that Chst14 gene deletion induces changes in the spinal cord and nervous system functions [ 1 , 8 , 13 ] as well as an abnormality of blood capillaries in the placenta [ 18 ] of mice. However, a model animal that focuses on the skin and bone (tissues related to serious symptoms of mcEDS- CHST14 ) has not been reported.…”

Section: Discussionmentioning

confidence: 99%

Backcrossing to an appropriate genetic background improves the birth rate of carbohydrate sulfotransferase 14 gene-deleted mice

et al. 2020

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Ehlers–Danlos syndromes (EDSs) are heterogeneous group of heritable connective tissue disorders characterized by joint and skin hyperextensibility as well as fragility of various organs. Recently, we described a new type of EDS, musculocontractual EDS (mcEDS- CHST14 ), caused by pathogenic variants of the carbohydrate sulfotransferase 14 ( CHST14 ) gene mutation. B6;129S5- Chst14 tm1Lex /Mmucd (B6;129- Chst14 KO) mice are expected to be an animal model of mcEDS- CHST14 . However, >90% of B6;129- Chst14 KO homozygous (B6;129- Chst14 −/− ) mice show perinatal lethality. Therefore, improvement of the birth rate of Chst14 −/− mice is needed to clarify the pathophysiology of mcEDS- CHST14 using this animal model. Some B6;129- Chst14 −/− embryos had survived at embryonic day 18.5 in utero , suggesting that problems with delivery and/or childcare may cause perinatal lethality. However, in vitro fertilization and egg transfer did not improve the birth rate of the mice. A recent report showed that backcrossing to C57BL/6 strain induces perinatal death of all Chst14 −/− mice, suggesting that genetic background influences the birthrate of these mice. In the present study, we performed backcrossing of B6;129- Chst14 KO mice to a BALB/c strain, an inbred strain that shows lower risks of litter loss than C57BL/6 strain. Upon backcrossing 1 to 12 times, the birth rate of Chst14 −/− mice was improved with a birth rate of 6.12–18.64%. These results suggest that the genetic background influences the birth rate of Chst14 −/− mice. BALB/c congenic Chst14 −/− (BALB. Chst14 −/− ) mice may facilitate investigation of mcEDS- CHST14 . Furthermore, backcrossing to an appropriate strain may contribute to optimizing animal experiments.

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Germline ablation of dermatan-4O-sulfotransferase1 reduces regeneration after mouse spinal cord injury

Cited by 14 publications

References 54 publications

Knockdown of chondroitin‐4‐sulfotransferase‐1, but not of dermatan‐4‐sulfotransferase‐1, accelerates regeneration of zebrafish after spinal cord injury

Knockdown of chondroitin‐4‐sulfotransferase‐1, but not of dermatan‐4‐sulfotransferase‐1, accelerates regeneration of zebrafish after spinal cord injury

Confocal Synaptology: Synaptic Rearrangements in Neurodegenerative Disorders and upon Nervous System Injury

Backcrossing to an appropriate genetic background improves the birth rate of carbohydrate sulfotransferase 14 gene-deleted mice

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