Evaluation of the gastrointestinal tract in <i>mdx</i> mice: an experimental model of Duchenne muscular dystrophy

Feder, David; Ierardi, Mariana Gameiro; Covre, Ana Laura; Petri, Giuliana; Carvalho, Alzira Alves de Siqueira; Fonseca, Fernando Luiz Affonso; Bertassoli, Bruno Machado

doi:10.1111/apm.12864

Cited by 6 publications

(17 citation statements)

References 27 publications

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“…Acute loperamide administration indeed slowed whole gut transit and decreased the number of produced pellets. Interestingly, we found that our control transit group had slower whole gut transit times than many reported in the literature, 11‐18 and we noted high pellet output in the early time points. Thus, we hypothesized that the faster transit times reported elsewhere might be due to the disruption of animal behavior during measurements.…”

Section: Discussionsupporting

confidence: 45%

A simple automated approach to measure mouse whole gut transit

Kacmaz

Alto

Knutson

et al. 2020

Neurogastroenterology Motil

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Background Gastrointestinal (GI) motility is a complex physiological process that is critical for normal GI function. Disruption of GI motility frequently occurs in GI diseases or as side effects of therapeutics. Whole gut transit measurements, like carmine red leading‐edge transit, in mice form the cornerstone of in vivo preclinical GI motility studies. Method We have developed an easily achievable, labor‐saving method to measure whole gut transit time in mice. This approach uses inexpensive, commercially available materials to monitor pellet production over time via high definition cameras capturing time‐lapse video for offline analysis. Key Result We describe the assembly of our automated gut transit setup and validate this approach by comparing the results with loperamide to delay transit and conventional transit measurements. We demonstrate that compared to the control group, the loperamide group had slowed transit, evidenced by a decrease in total pellet production and prolonged whole gut transit time. The control group had an extended transit time compared with the results reported in the literature. Whole gut transit rates accelerated to times comparable to the literature by disrupting cages every 10‐15 min to imitate the conventional approach, suggesting that disruption affects the assay and supports the use of an automated approach. Conclusion & Inferences A novel automated, inexpensive, and easily assembled whole gut transit setup is labor‐saving and allows minimal disruption to animal behavior compared with the conventional approach.

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Section: Discussionsupporting

confidence: 45%

A simple automated approach to measure mouse whole gut transit

Kacmaz

Alto

Knutson

et al. 2020

Neurogastroenterology Motil

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“…Colonic motility was examined by quantifying faecal pellet output over an 8 h period following gavage with carmine red [32], which is not absorbed from the lumen of the gut. Carmine red (300 µL per mouse; 6%; Sigma-Aldrich, Taufkirchen, Germany) was suspended in 0.5% methylcellulose (Sigma-Aldrich, Taufkirchen, Germany) and administered via oral gavage.…”

Section: Gut Motilitymentioning

confidence: 99%

“…GI symptoms are relatively common in people with PD and can include constipation or a delay in gastric emptying [46,47]. In order to examine gut motility in our model, we administered a non-absorbable dye (carmine red) and then monitored faecal pellet output over a period of 8 h. This is a well-validated test that has been used in humans [48] and rodents [32,49]. No difference in latency to expel red faecal pellets was observed (Figure 6A, time x treatment F (3, 60) = 1.7, ns).…”

Section: Intrastriatal Rotenone Causes No Change In Gastrointestinal ...mentioning

confidence: 99%

No Evidence of Sensory Neuropathy in a Traditional Mouse Model of Idiopathic Parkinson’s Disease

Faisal,

Rusetskaya,

Väli

et al. 2024

Cells

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Parkinson’s disease (PD) is the second-most common neurodegenerative disorder worldwide and is diagnosed based on motor impairments. Non-motor symptoms are also well-recognised in this disorder, and peripheral neuropathy is a frequent but poorly appreciated non-motor sign. Studying how central and peripheral sensory systems are affected can contribute to the development of targeted therapies and deepen our understanding of the pathophysiology of PD. Although the cause of sporadic PD is unknown, chronic exposure to the pesticide rotenone in humans increases the risk of developing the disease. Here, we aimed to investigate whether peripheral neuropathy is present in a traditional model of PD. Mice receiving intrastriatal rotenone showed greatly reduced dopamine terminals in the striatum and a reduction in tyrosine hydroxylase-positive neurons in the Substantia nigra pars compacta and developed progressive motor impairments in hindlimb stepping and rotarod but no change in spontaneous activity. Interestingly, repeated testing using gold-standard protocols showed no change in gut motility, a well-known non-motor symptom of PD. Importantly, we did not observe any change in heat, cold, or touch sensitivity, again based upon repeated testing with well-validated protocols that were statistically well powered. Therefore, this traditional model fails to replicate PD, and our data again reiterate the importance of the periphery to the disorder.

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“…Furthermore, the mdx mice have a higher concentration of collagen fibers in the submucosal region of the GI tract than wild-type (WT) mice. These alterations are presumably consequences of the loss of dystrophin protein [17][18][19].…”

Section: Introductionmentioning

confidence: 99%

Pathological alterations in the gastrointestinal tract of a porcine model of DMD

et al. 2021

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Background Patients with Duchenne muscular dystrophy (DMD) develop severe skeletal and cardiac muscle pathologies, which result in premature death. Therefore, the current therapeutic efforts are mainly targeted to correct dystrophin expression in skeletal muscle and heart. However, it was reported that DMD patients may also exhibit gastrointestinal and nutritional problems. How the pathological alterations in gastrointestinal tissues contribute to the disease are not fully explored. Results Here we employed the CRISPR/Cas9 system combined with somatic nuclear transfer technology (SCNT) to establish a porcine model of DMD and explored their pathological alterations. We found that genetic disruption of dystrophin expression led to morphological gastrointestinal tract alterations, weakened the gastrointestinal tract digestion and absorption capacity, and eventually led to malnutrition and gastric dysfunction in the DMD pigs. Conclusions This work provides important insights into the pathogenesis of DMD and highlights the need to consider the gastrointestinal dysfunction as an additional therapeutic target for DMD patients.

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Evaluation of the gastrointestinal tract in mdx mice: an experimental model of Duchenne muscular dystrophy

Cited by 6 publications

References 27 publications

A simple automated approach to measure mouse whole gut transit

A simple automated approach to measure mouse whole gut transit

No Evidence of Sensory Neuropathy in a Traditional Mouse Model of Idiopathic Parkinson’s Disease

Pathological alterations in the gastrointestinal tract of a porcine model of DMD

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