Morphological abnormalities in the brains of estrogen receptor beta knockout mice

Estrogen receptor beta (ER beta) is expressed at high levels in both neuron s and glial cells of the central nervous system. The development of ER beta knockout (BERKO) mice has provided a model to study the function of this n uclear receptor in the brain. We have found that the brains of BERKO mice s how several morphological abnormalities. There is a regional neuronal hypoc ellularity in the brain, with a severe neuronal deficit in the somatosensor y cortex, especially layers II, III, IV, and V, and a remarkable proliferat ion of astroglial cells in the limbic system but not in the cortex. These a bnormalities are evident as early as 2 mo of age in BERKO mice. As BERKO mi ce age, the neuronal deficit becomes more pronounced, and, by 2 yr of age, there is degeneration of neuronal cell bodies throughout the brain. This is particularly evident in the substantia nigra. We conclude that ER beta is necessary for neuronal survival and speculate that this gene could have an important influence on the development of degenerative diseases of the cent ral nervous system, such as Alzheimer's disease and Parkinson's disease, as well as those resulting from trauma and stroke in the brain.