A Neonatal BALB/c Mouse Model of Necrotizing Enterocolitis
Summary
Necrotizing enterocolitis (NEC) is the most severe gastrointestinal (GI) disease that often occurs in premature infants, especially very low birth weight infants, with high mortality and unclear pathogenesis. The cause of NEC may be related to inflammatory immune regulatory system abnormalities. An NEC animal model is an indispensable tool for NEC disease immune research. NEC animal models usually use C57BL/6J neonatal mice; BALB/c neonatal mice are rarely used. Related studies have shown that when mice are infected, Th2 cell differentiation is predominant in BALB/c mice compared to C57BL/6J mice. Studies have suggested that the occurrence and development of NEC are associated with an increase in T helper type 2 (Th2) cells and are generally accompanied by infection. Therefore, this study used neonatal BALB/c mice to induce an NEC model with similar clinical characteristics and intestinal pathological changes as those observed in children with NEC. Further study is warranted to determine whether this animal model could be used to study Th2 cell responses in NEC.
Abstract
Necrotizing enterocolitis (NEC) is the most severe gastrointestinal (GI) disease that often occurs in premature infants, especially very low birth weight infants, with high mortality and unclear pathogenesis. The cause of NEC may be related to inflammatory immune regulatory system abnormalities. An NEC animal model is an indispensable tool for NEC disease immune research. NEC animal models usually use C57BL/6J neonatal mice; BALB/c neonatal mice are rarely used. Related studies have shown that when mice are infected, Th2 cell differentiation is predominant in BALB/c mice compared to C57BL/6J mice. Studies have suggested that the occurrence and development of NEC are associated with an increase in T helper type 2 (Th2) cells and are generally accompanied by infection. Therefore, this study used neonatal BALB/c mice to induce an NEC model with similar clinical characteristics and intestinal pathological changes as those observed in children with NEC. Further study is warranted to determine whether this animal model could be used to study Th2 cell responses in NEC.
Introduction
Necrotizing enterocolitis (NEC), the most severe gastrointestinal (GI) disease, occurs in most premature infants (>90%), especially those with very low birth weight (VLBW)1. In VLBW infants, the incidence of the disease ranges from 10% to 12%, and the mortality of children diagnosed with NEC is between 20% and 30%2,3. The cause of NEC may be related to mucosal injuries, invasion by pathogenic bacteria, and intestinal feeding, which can lead to inflammatory responses and the induction of intestinal injuries in susceptible hosts3. The pathogenesis of NEC is unclear. Relevant research shows that the affected infant's immune response is abnormal, and genetic susceptibility, microvascular tension, and intestinal bacterial changes may play important roles in the disease3.
The NEC animal model is an indispensable tool for research on the pathogenesis of NEC. The animal species used for NEC models are pigs, rats, and mice. However, due to the long gestation period, growth cycles, and high costs, in recent years, pigs have not been the first choice for NEC models and have been replaced with rats or mice4. As there are differences in the immune background of different mouse strains5, different studies need to use different strains of mice to establish NEC animal models. BALB/c mice have an important feature; when they are infected or cope with external damage, the polarization of TH2 cells during infection in mice is significantly stronger than that in other strains of mice6,7,8. T helper cells play a crucial role in the occurrence and progression of NEC, especially the development of TH2 cells3,9,10,11. Therefore, this study used BALB/c mice to establish the NEC model, which might be helpful for NEC disease research on T cells.
Protocol
Representative Results
Discussion
NEC is the most common gastrointestinal system emergency for neonates, with a high incidence and mortality, especially in premature infants1,2,3. However, its pathogenesis is still unclear. It is currently believed that mucosal damage, pathogen invasion, and enteral feeding are high-risk factors for NEC3. To date, the animals used for the NEC model are mainly pigs, rats, and mice. Most studies have used n…
Disclosures
The authors have nothing to disclose.
Acknowledgements
The authors thank the Clinical Biological Resource Bank of Guangzhou Women and Children's Medical Center for providing the clinical sample and Guangzhou Forevergen Biosciences Laboratory Animal Center for providing mice. This research was supported by the National Natural Science Foundation of China grant 81770510 (R.Z.).
Materials
| Absolute ethanol | Sinopharm Chemical Reagent Co., LTD. | 100092683 | |
| Goat Milk powder | Petag | 71795558417 | |
| HE dye solution | Sinopharm Chemical Reagent Co., LTD. | G1003 | |
| Isoflurane | RWD, Shenzhen Reward Life Technology Co., LTD. | R510 | |
| LPS | Sigma-Adrich | L2880 | |
| Medical oxygen | various | various | |
| Microscope | NIKON | NIKON imaging system (DS-Ri2) | |
| Neutral resin | Sinopharm Chemical Reagent Co., LTD. | 10004160 | |
| Paraffin | various | various | |
| Premature baby milk powder | Abbott | 57430 | |
| Xylene | Sinopharm Chemical Reagent Co., LTD. | 10023418 | |
| 1% Hydrochloric acid | various | various | |
| 10% Formalin | LEAGENE | DF0110 |
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