Sudden infant death syndrome (SIDS) is one of the leading causes of post-neonatal infant mortality in the western world, affecting 0.6/100 live births. Epidemiological data, which have identified risk factors (unsafe sleep environment, prematurity, and others) and point to a peak incidence from ~2-4 months of age, are the root of the Triple Risk Hypothesis of SIDS - an infant with and underlying biological vulnerability, when combined with an exogenous stressor during a critical developmental period result in SIDS. While it remains unclear, there are several pieces of data that implicate dysfunction in the brainstem 5-HT system in SIDS.
We in the Hodges Lab are focused on determining what the underlying biological vulnerability may be in SIDS. We do this by studying ventilatory and temperature control in animal models of serotonin system dysfunction. Along with our collaborators in the Lab of Aron Geurts, we targeted exon 7 of the tryptophan hydroxylase 2 (Tph2) gene for mutation using zinc finger nucleases (ZFNs; see also Kaplan et al., 2016). The resulting Tph2 knockout (DATph2-/-) rat lines failed to show Tph2 immunoreactivity and had no measurable 5-HT (or HIAA) in the central nervous system. DATph2-/- rats also have reduced body weights, increased mortality, reduced ventilation and increased breathing variability, and reduced body temperatures during post-natal development.
Thus, we aim to further test the Triple Risk Model of SIDS using these and other animal models of brainstem 5-HT dysfunction. If you are interested in this work, please contact the lab using the link below.