Characterization of microminipig as a laboratory animal for safety pharmacology study by analyzing fluvoxamine-induced cardiovascular and dermatological adverse reactions

Tanikawa, Yoichi; Hagiwara-Nagasawa, Mihoko; Kambayashi, Ryuichi; Goto, Ai; Chiba, Koki; Kitta, Kumiko; Hoshiai, Kiyotaka; Izumi-Nakaseko, Hiroko; Naito, Atsuhiko T.; Sugiyama, Atsushi

doi:10.1007/s12012-019-09509-w

Cited by 5 publications

(5 citation statements)

References 25 publications

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“…As their body weight at maturity is~10 kg, large-scale breeding facilities are unnecessary, smaller amount of reagents are sufficient in experiments, and handling is easy. For these reasons, their usage as well as the number of studies using this animal model is rapidly increasing in various fields including pharmacology [29], gene doping [30], and viral infection [31]. Therefore, evaluating the utility of microminipigs as a new animal model for gene expression is of vital significance.…”

Section: Introductionmentioning

confidence: 99%

Utility of microminipigs for evaluating liver-mediated gene expression in the presence of neutralizing antibody against vector capsid

et al. 2020

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Adeno-associated virus (AAV) vectors can transduce hepatocytes efficiently in vivo in various animal species, including humans. Few reports, however, have examined the utility of pigs in gene therapy. Pigs are potentially useful in preclinical studies because of their anatomical and physiological similarity to humans. Here, we evaluated the utility of microminipigs for liver-targeted gene therapy. These pigs were intravenously inoculated with an AAV8 vector encoding the luciferase gene, and gene expression was assessed by an in vivo imaging system. Robust transgene expression was observed almost exclusively in the liver, even though the pig showed a low-titer of neutralizing antibody (NAb) against the AAV8 capsid. We assessed the action of NAbs against AAV, which interfere with AAV vector-mediated gene transfer by intravascular delivery. When a standard dose of vector was administered intravenously, transgene expression was observed in both NAbnegative and low-titer (14×)-positive subjects, whereas gene expression was not observed in animals with higher titers (56×). These results are compatible with our previous observations using nonhuman primates, indicating that pigs are useful in gene therapy experiments, and that the role of low-titer NAb in intravenous administration of the AAV vector shows similarities across species.

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Section: Introductionmentioning

confidence: 99%

Utility of microminipigs for evaluating liver-mediated gene expression in the presence of neutralizing antibody against vector capsid

et al. 2020

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“…Minipigs are one of the major animal species used in translational research because of their similarities with humans in anatomical and physiological characteristics. 1,2 Among several strains of minipigs, microminipigs (Fuji Micra Inc, Shizuoka, Japan) have become an increasingly attractive animal model and have been used in pharmacological and toxicological studies, 3 –7 human disease models, 8 –11 and studies of regenerative medicine. 12,13 In addition, microminipigs have considerable potential, particularly for long-term studies, because of their manageable size, reaching approximately 10 kg at sexual maturity and up to 20 to 30 kg at adulthood.…”

Section: Introductionmentioning

confidence: 99%

Spontaneous Age-Related Histopathological Changes in Microminipigs

Kangawa

Nishimura²,

Nishimura³

et al. 2019

Toxicol Pathol

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Microminipigs have become an attractive animal model for toxicology and pharmacology studies and for human disease models, owing to their manageable size. Although there are numerous reports of spontaneous age-related lesions in mice, rats, dogs, and monkeys, those in minipigs are scarce. In the present study, spontaneous age-related histopathological changes were investigated using 37 microminipigs (20 males and 17 females) that were 6 months to 10 years of age. Abnormal deposits of materials were evident in several animals from 6 years of age, and these deposits included amyloid in the renal medulla, thyroid gland, and adrenal gland, hyaline droplets in glomeruli, and fibrillar inclusions in neurons. Arterial sclerosing changes (intimal thickening, intimal proliferation, and medial mineralization) and proliferative lesions (hyperplasia of hepatocytes, follicular cells, Leydig cells, and uterine endometrial glands) were present at 4 years of age and beyond. Renal adenoma, uterine leiomyoma, and Leydig cell tumor were observed in several microminipigs. Moreover, glomerulosclerosis, renal interstitial fibrosis, thymic involution, and adrenocortical cell vacuolation were common in aging microminipigs. Since knowledge of age-related changes is helpful for pathologists, the basic information obtained in this study will be a useful reference for all future toxicity evaluations in microminipigs.

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“…In the 2000s, crossbreeding of various miniature pigs including Pot-bellied pig for further miniaturization led to creation of microminipig , a super-compact miniature pig weighing about 10 kg, which can be about the same weight as a beagle dog, and easy to handle [ 5 ]. Accordingly, microminipig is expected as a new experimental animal of non-rodent species optimized for life science research [ 2 , 3 , 7 , 11 , 15 , 16 ]. Here, we showed the effects of body size reduction on electrocardiographic indices in microminipig in comparison with those in Clawn miniature swine, one of the well-established laboratory animals, since such information is still limited within a species of swine.…”

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confidence: 99%

Characterization of the electrocardiogram of <i>microminipig</i> in comparison with that of Clawn miniature swine: impacts of miniaturization of body size on electrocardiographic indices

Goto

Kambayashi

Saito

et al. 2023

The Journal of Veterinary Medical Science

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Effects of body size reduction on electrocardiographic indices were examined using microminipigs in comparison with Clawn miniature swine (Clawn). Electrocardiogram was recorded using Holter electrocardiograph in conscious state for 24 hr for microminipigs (male: 11.6 ± 0.1 kg, 12–17 months, n=5; and female: 9.9 ± 0.4 kg, 6 months, n=5) and Clawn (female: 20.3 ± 0.4 kg, 8–9 months, n=8). Microminipig had shorter PR interval and QRS width than Clawn, whereas no significant difference was detected in JTcF/QTcF between them. Ratios of PR interval, QRS width, and body weight cubic root for microminipigs to Clawn ranged between 0.713 and 0.830. These findings indicate that PR interval and QRS width will depend on distance for excitatory current propagation, whereas JTcF/QTcF may be governed by local electrical activities.

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Characterization of microminipig as a laboratory animal for safety pharmacology study by analyzing fluvoxamine-induced cardiovascular and dermatological adverse reactions

Cited by 5 publications

References 25 publications

Utility of microminipigs for evaluating liver-mediated gene expression in the presence of neutralizing antibody against vector capsid

Utility of microminipigs for evaluating liver-mediated gene expression in the presence of neutralizing antibody against vector capsid

Spontaneous Age-Related Histopathological Changes in Microminipigs

Characterization of the electrocardiogram of <i>microminipig</i> in comparison with that of Clawn miniature swine: impacts of miniaturization of body size on electrocardiographic indices

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