A decrease in size and number of basal forebrain cholinergic neurons is paralleled by diminished hippocampal cholinergic innervation in mice lacking leukocyte common antigen related protein tyrosine phosphatase activity
Emm. Van Lieshout et al., A decrease in size and number of basal forebrain cholinergic neurons is paralleled by diminished hippocampal cholinergic innervation in mice lacking leukocyte common antigen related protein tyrosine phosphatase activity, NEUROSCIENC, 102(4), 2001, pp. 833-841
The leukocyte common antigen-related (LAR) receptor, composed of an extrace
llular region with three immunoglobulin-like and eight fibronectin type III
-like domains, and a cytoplasmic region containing two protein tyrosine pho
sphatase domains, is thought to play a role in axonal outgrowth and guidanc
e during neural development. LAR mutant mice were generated completely tack
ing the two cytoplasmic protein tyrosine phosphatase domains, resulting in
the loss of ability to bind intracellular associating proteins, but (may be
) still containing the ability to perform extracellular functions. A reduct
ion in size of basal forebrain cholinergic neurons and diminished hippocamp
al innervation reponed for knockout mice that contain a leaky gene trap ins
erted into the 5' part of the LAR gene [Yeo T. T. et al. (1997) J. Neurusci
. Res. 47, 348-360] warranted a computer-assisted quantitative image analys
is throughout the basal forebrain and hippocampus of our LAR mutant mice. T
he total number, longest diameter and cell body area were calculated for th
e choline acetyltransferase-positive neurons in the medial septum and verti
cal diagonal band, and optical density measurements were performed to deter
mine the extent of acetyl cholinesterase-positive fibre innervation of the
different layers in the dentate gyrus. In LAR mutant mice, the number of ch
olinergic cells was significantly reduced (similar to 25%) in the vertical
diagonal band. Also. the cross-sectional area of the cholinergic neurons in
the medial septum and vertical diagonal band was reduced (5%). These findi
ngs were paralleled by a diminished cholinergic innervation of the supragra
nular (18%) and molecular (4%) layers of the dentate gyrus.
Thus, LAR protein tyrosine phosphatase activity appears crucial for size, n
umber and target projection of basal forebrain cholinergic neurons, further
strengthening a role for LAR in CNS development. (C) 2001 IBRO. Published
by Elsevier Science Ltd. All rights reserved.