Comparative functional analysis of mice after local injection with botulinum neurotoxin A1, A2, A6, and B1 by catwalk analysis

Moritz, Molly S.; Tepp, William H.; Inzalaco, Heather N'te; Johnson, Eric A.; Pellett, Sabine

doi:10.1016/j.toxicon.2019.06.004

Cited by 13 publications

(9 citation statements)

References 76 publications

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“…Gait was analyzed using the CatWalk XT system (Noldus Information Technology) essentially as described in ( 48 ) with the following exceptions: Mice were not trained to reach a goal box but to directly reach the homecage. Training was performed on the first day and the test was done on two consecutive days directly after the training day.…”

Section: Methodsmentioning

confidence: 99%

The HUSH complex controls brain architecture and protocadherin fidelity

et al. 2022

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The HUSH (human silencing hub) complex contains the H3K9me3 binding protein M-phase phosphoprotein 8 (MPP8) and recruits the histone methyltransferase SETDB1 as well as Microrchidia CW-type zinc finger protein 2 (MORC2). Functional and mechanistic studies of the HUSH complex have hitherto been centered around SETDB1 while the in vivo functions of MPP8 and MORC2 remain elusive. Here, we show that genetic inactivation of Mphosph8 or Morc2a in the nervous system of mice leads to increased brain size, altered brain architecture, and behavioral changes. Mechanistically, in both mouse brains and human cerebral organoids, MPP8 and MORC2 suppress the repetitive-like protocadherin gene cluster in an H3K9me3-dependent manner. Our data identify MPP8 and MORC2, previously linked to silencing of repetitive elements via the HUSH complex, as key epigenetic regulators of protocadherin expression in the nervous system and thereby brain development and neuronal individuality in mice and humans.

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Section: Methodsmentioning

confidence: 99%

The HUSH complex controls brain architecture and protocadherin fidelity

et al. 2022

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“…A majority of botulinum neurotoxin sub-types have been identified through the sequencing of genes encoding botulinum neurotoxins, and the derivation of the amino acid sequence. Most sub-types differ by at least 2.6% in amino acid sequence from another sub-type [ 45 , 46 ], and sub-types of botulinum neurotoxins serotypes A and B have been shown to exhibit distinct functional and toxicological properties [ 47 , 48 , 49 , 50 , 51 ]. Each botulinum neurotoxin sub-type comprises a series of variants with unique amino acid sequence.…”

Section: Introductionmentioning

confidence: 99%

Diversity of the Genomes and Neurotoxins of Strains of Clostridium botulinum Group I and Clostridium sporogenes Associated with Foodborne, Infant and Wound Botulism

Brunt

Vliet

Carter

et al. 2020

Toxins

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Clostridium botulinum Group I and Clostridium sporogenes are closely related bacteria responsible for foodborne, infant and wound botulism. A comparative genomic study with 556 highly diverse strains of C. botulinum Group I and C. sporogenes (including 417 newly sequenced strains) has been carried out to characterise the genetic diversity and spread of these bacteria and their neurotoxin genes. Core genome single-nucleotide polymorphism (SNP) analysis revealed two major lineages; C. botulinum Group I (most strains possessed botulinum neurotoxin gene(s) of types A, B and/or F) and C. sporogenes (some strains possessed a type B botulinum neurotoxin gene). Both lineages contained strains responsible for foodborne, infant and wound botulism. A new C. sporogenes cluster was identified that included five strains with a gene encoding botulinum neurotoxin sub-type B1. There was significant evidence of horizontal transfer of botulinum neurotoxin genes between distantly related bacteria. Population structure/diversity have been characterised, and novel associations discovered between whole genome lineage, botulinum neurotoxin sub-type variant, epidemiological links to foodborne, infant and wound botulism, and geographic origin. The impact of genomic and physiological variability on the botulism risk has been assessed. The genome sequences are a valuable resource for future research (e.g., pathogen biology, evolution of C. botulinum and its neurotoxin genes, improved pathogen detection and discrimination), and support enhanced risk assessments and the prevention of botulism.

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“…Previous studies have shown that toxin potency differences can exist between different BoNT subtypes within one serotype [ 63 , 70 , 71 , 72 , 73 , 74 ]. For example, BoNT/A1 has about 1000-fold higher activity in mice compared to BoNT/A4, while BoNT/A3 appears to have a shorter duration of action than other BoNT/A subtypes 1–5 [ 70 , 71 ].…”

Section: Discussionmentioning

confidence: 99%

Genomic Diversity, Competition, and Toxin Production by Group I and II Clostridium botulinum Strains Used in Food Challenge Studies

et al. 2022

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Botulinum neurotoxins (BoNTs) produced by the bacteria Clostridium botulinum are the causative agent of human and animal botulism, a rare but serious and potentially deadly intoxication. Foodborne botulism is caused by the consumption of foods containing BoNTs, which results from contamination of foods with C. botulinum spores and toxin production by the bacteria during growth within the food. Validation of the safety of food products is essential in preventing foodborne botulism, however, limited guidance and standards exist for the selection of strains used in C. botulinum food challenge studies. Sequencing and genomics studies have revealed that C. botulinum is a large, diverse, and polyphyletic species, with physiologic and growth characteristics studied only in a few representatives. Little is known about potential growth competition or effects on toxin production between C. botulinum strains. In this study, we investigated an applied cocktail of ten C. botulinum strains, seven Group I and three Group II. Whole genome SNP alignments revealed that this strain cocktail encompasses the major clades of the Group I and II C. botulinum species. While growth competition appears to exist between several of the strains, the cocktail as a whole resulted in high levels of BoNT production.

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Comparative functional analysis of mice after local injection with botulinum neurotoxin A1, A2, A6, and B1 by catwalk analysis

Cited by 13 publications

References 76 publications

The HUSH complex controls brain architecture and protocadherin fidelity

The HUSH complex controls brain architecture and protocadherin fidelity

Diversity of the Genomes and Neurotoxins of Strains of Clostridium botulinum Group I and Clostridium sporogenes Associated with Foodborne, Infant and Wound Botulism

Genomic Diversity, Competition, and Toxin Production by Group I and II Clostridium botulinum Strains Used in Food Challenge Studies

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