Lack of the protein tyrosine phosphatase SHP-1 results in decreased numbers of glia within the motheaten (me/me) mouse brain

Mice that are homozygous for the autosomal recessive motheaten allele (me/m e) lack the protein tyrosine phosphatase SHP-1. Loss of SHP-1 leads to many hematopoietic abnormalities, as well as defects such as infertility and lo w body weight. However, little is known regarding the role SHP-1 plays in t he development of the central nervous system (CNS). To define the role of S HP-1 in CNS development and differentiation, we examined the brains of me/m e mice at various times after birth for neuronal and glial abnormalities. A lthough the brains of me/me mice are slightly smaller than age-matched wild -type littermates, both me/me and wild-type brains are similar in weight, p ossess an intact blood-brain barrier, and have largely normal neuronal arch itecture. Significantly, the current study reveals that me/me brain shows d ecreases in the number of glial fibriallary acidic protein (GFAP) + astrocy tes and F480+ microglia compared with wild-type mice. In addition, decrease d immunostaining for the myelin-synthesizing enzyme CNPase was observed in me/me mice, confirming the loss of myelin in these animals, as reported (Ma ssa et al. [2000] Glia 29:376-385). It is particularly significant that the re is a decreased number of immunolabeled glia of all subtypes and that thi s deficit in glial number is not restricted to a particular class of glia. This suggests that SHP-1 is necessary for the normal differentiation and di stribution of astrocytes, microglia, and oligendrocytes within the murine C NS. J. Comp. Neurol. 441:118-133,2001. (C) 2001 Wiley-Liss, Inc.