Molecular, morphometric and functional analyses demonstrate that the growth hormone deficient little mouse is not hypomyelinated.

ABSTRACT

To study the effects of naturally occurring growth hormone deficiency type I on CNS myelination, we compared the myelination of brains from little and wild-type littermate mice using molecular, histological, morphometric, and functional analyses. The little mouse produces only 6-8% of normal levels of growth hormone (GH) and approximately 20% of normal circulating levels of insulin-like growth factor 1 (IGF-1). Our data show that the expression of myelin basic protein (MBP) and proteolipid protein (PLP) of the little brain exhibit the same temporal pattern and amount as that of the wild-type brain. Furthermore, the density and size of myelinated axons and the myelin sheath thickness in the corpus callosum, anterior commissure and the optic nerve are comparable in the little and wild-type brains. These regions are reduced in size in the little mouse brain proportionate to the overall reduction in brain size implying a reduction in the total number of neurons. Therefore, it follows that the total myelin content is reduced, but when normalized to brain size, the myelin concentration is unchanged. Myelin staining patterns of whole brains were identical. Moreover, functional analysis of the visual pathway indicated no difference between the little and control mice. These results are inconsistent with previous reports of hypomyelination in the little mouse and suggest that this form of GH deficiency does not adversely affect the myelination process except possibly through neuronal proliferation. However, since axon size and density are maintained, the neuronal growth may conversely be inherently limited by other restricted brain growth.