A Possible Murine Model for Investigation of Pathogenesis of Sudden Infant Death Syndrome

Abstract

Several studies have indicated a possible causative role of toxigenic bacteria in sudden infant death syndrome (SIDS). This study examined the effect of toxigenic E. coli on pregnant and infant mice to determine if these animals could be used as a model for SIDS pathogenesis. Strains of E. coli from the intestinal contents of infants who have died of SIDS or other causes and from the faeces of healthy infants were collected over a broad time scale. The isolates were tested for their ability to produce then known toxins of E. coli and were serotyped (O and H antigens). Certain serotypes (e.g. O1:H- and O25:H1) emerged significantly more frequently from cases of SIDS than from healthy infants and isolates of these types were generally toxigenic in Vero-cell cultures but whose verotoxicity was not related to classical Shiga or other known toxins. This mouse model was developed to test the effects of these toxigenic and also non-toxigenic strains. Four apparently healthy pups aged between 17 and 21 days died unobserved overnight but no pups of the 54 control mice died suddenly (P = 0.0247, Fisher's exact test). These were considered to represent sudden unexpected deaths. Pathological effects compatible with those in SIDS were observed in mouse pups exposed to toxigenic strains indicating this model may be suitable for further study into the pathogenesis of unexpected deaths in infancy. Providing an animal model of SIDS would promote a much better avenue for studying the pathogenesis of this enigmatic condition.

SIDS Risk Factors: Time for New Interpretations. The Role of Bacteria

“…We have demonstrated that a SIDS-like condition can be established in a murine model (Bettelheim et al 2012). This and the significant work on interactions between cigarette smoke, virus infection and responses to bacterial toxins that has been carried out by Blood Siegfried and colleagues (2004) in a rat pup model as well as the earlier studies by Jakeman et al (1991) should provide important answers to the underlying mechanisms and the various parameters can be studied in detail.…”

Animal Models for Assessment of Infection and Inflammation: Contributions to Elucidating the Pathophysiology of Sudden Infant Death Syndrome

“…Dams exposed to the toxigenic strain had smaller litter sizes and some runting of the pups. Mortality was 18% for the SIDS E. coli strain compared to 9% for non-SIDS isolates ( 33 ) (Table 1 ). In a different mouse model, gamma herpes virus plus a non-lethal dose of endotoxin was responsible for a reduction of litter size and fetal loss ( 34 ) (Table 1 ).…”

“…Prone sleeping position plays a significant role in SIDS risk, not because of its effect on normal oxygen/carbon dioxide-exchange but rather on an increase in temperature. Elevated body temperature and increased toxin production by bacterial isolates in the nasal pharynx might be a contributing factor ( 33 , 63 , 64 ). Data suggest that prone position will exacerbate the consequences of a viral infection because it promotes an optimum temperature to increase the numbers and variety of bacterial species in upper respiratory secretions and stimulates bacterial toxin production ( 65 ).…”

Sudden Infant Death Syndrome, Infection, Prone Sleep Position, and Vagal Neuroimmunology

“…In favor of a gut origin was the finding of non-Shiga toxin verotoxigenic Escherichia coli belonging to a restricted range of serogroups not seen in live matched control babies ( 15 ). In addition, these E. coli were capable of causing death in neonatal mouse pups ( 4 ). These studies led us to explore the role of the gut microbiome in SIDS, which gave us interesting preliminary findings ( 16 ).…”