Bilirubin-induced neurologic dysfunction (BIND) and kernicterus has been used to 
describe moderate to severe neurologic dysfunction observed in children exposed 
to excessive levels of total serum bilirubin (TSB) during the neonatal period. 
Here we use a new mouse model that targets deletion of the Ugt1 locus and the 
Ugt1a1 gene in liver to promote hyperbilirubinemia-induced seizures and central 
nervous system toxicity. The accumulation of TSB in these mice leads to diffuse 
yellow coloration of brain tissue and a marked cerebellar hypoplasia that we 
characterize as kernicterus. Histologic studies of brain tissue demonstrate that 
the onset of severe neonatal hyperbilirubinemia, characterized by seizures, 
leads to alterations in myelination and glia reactivity. Kernicterus presents as 
axonopathy with myelination deficits at different brain regions, including pons, 
medulla oblongata, and cerebellum. The excessive accumulation of TSB in the 
early neonatal period (5 days after birth) promotes activation of the myelin 
basic protein (Mbp) gene with an accelerated loss of MBP that correlates with a 
lack of myelin sheath formation. These changes were accompanied by increased 
astroglial and microglial reactivity, possibly as a response to myelination 
injury. Interestingly, cerebellum was the area most affected, with greater 
myelination impairment and glia burden, and showing a marked loss of Purkinje 
cells and reduced arborization of the remaining ones. Thus, kernicterus in this 
model displays not only axonal damage but also myelination deficits and glial 
activation in different brain regions that are usually related to the neurologic 
sequelae observed after severe hyperbilirubinemia.