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/me) lack the protein tyrosine phosphatase SHP-1. Loss of SHP-1 leads to many hematopoietic abnormalities, as well as defects such as infertility and low body weight. However, little is known regarding the role SHP-1 plays in the development of the central nervous system (CNS). To define the role of SHP-1 in CNS development and differentiation, we examined the brains of me/me mice at various times after birth for neuronal and glial abnormalities. Although 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, possess an intact blood-brain barrier, and have largely normal neuronal architecture. Significantly, the current study reveals that me/me brain shows decreases in the number of glial fibriallary acidic protein (GFAP)+ astrocytes and F480+ microglia compared with wild-type mice. In addition, decreased immunostaining for the myelin-synthesizing enzyme CNPase was observed in me/me mice, confirming the loss of myelin in these animals, as reported (Massa et al. [2000] Glia 29:376-385). It is particularly significant that there is a decreased number of immunolabeled glia of all subtypes and that this 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 distribution of astrocytes, microglia, and oligendrocytes within the murine CNS.
Wishcamper
C A
CA
Department of Pharmaceutical Sciences, University of Montana, Missoula, MT 59812, USA.
Coffin
J D
JD
Lurie
D I
DI
D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism* / Q000473:pathology*; D000860:Hypoxia / Q000473:pathology; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D008818:Mice, Neurologic Mutants / Q000033:anatomy & histology* / Q000378:metabolism*; D009186:Myelin Sheath / Q000378:metabolism; D009457:Neuroglia / Q000473:pathology*; D009836:Oligodendroglia / Q000473:pathology; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases / Q000172:deficiency*
D047908:Intracellular Signaling Peptides and Proteins; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases; C516725:Ptpn11 protein, mouse; C509248:Ptpn6 protein, mouse