Deficient LAR expression decreases basal forebrain cholinergic neuronal size and hippocampal cholinergic innervation.
A role in neural development for protein tyrosine phosphatase (PTPase) receptors has been suggested by the finding of aberrant neurite outgrowth in Drosophila mutants lacking functional leukocyte common antigen-related (LAR) PTPase receptors; however, PTPase functions in the mammalian nervous system remain to be established. In transgenic mice containing a gene trap in the LAR gene, only trace expression of full-length LAR transcripts was found. In these mice, the size of basal forebrain cholinergic neurons was significantly reduced and cholinergic innervation of the dentate gyrus was markedly decreased. These findings constitute the first demonstration of an aberrant neuronal phenotype in a mammalian PTPase mutant and support the hypothesis that LAR-type PTPase receptors function to establish and/or maintain neuronal networks.
Yeo
T T
TT
Department of Neurology, UCSF/VA Medical Center, CA 94121, USA.
Yang
T
T
Massa
S M
SM
Zhang
J S
JS
Honkaniemi
J
J
Butcher
L L
LL
Longo
F M
FM
D000109:Acetylcholine / Q000502:physiology; D000818:Animals; D048588:Benzoxazines; D015415:Biomarkers; D015152:Blotting, Northern; D048429:Cell Size / Q000502:physiology; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D002799:Cholinergic Fibers / Q000737:chemistry / Q000201:enzymology; D004396:Coloring Agents; D018891:Dentate Gyrus / Q000737:chemistry / Q000166:cytology*; D005260:Female; D015870:Gene Expression / Q000502:physiology; D005838:Genotype; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009474:Neurons / Q000737:chemistry / Q000166:cytology / Q000502:physiology*; D010078:Oxazines; D010641:Phenotype; D016548:Prosencephalon / Q000166:cytology; D017027:Protein Tyrosine Phosphatases / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D054630:Receptor-Like Protein Tyrosine Phosphatases, Class 4; D011956:Receptors, Cell Surface / Q000235:genetics; D017475:Receptors, Nerve Growth Factor / Q000032:analysis
D048588:Benzoxazines; D015415:Biomarkers; D004396:Coloring Agents; D010078:Oxazines; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D017475:Receptors, Nerve Growth Factor; C028911:cresyl violet; D002795:Choline O-Acetyltransferase; D017027:Protein Tyrosine Phosphatases; C516843:Ptpra protein, mouse; D054630:Receptor-Like Protein Tyrosine Phosphatases, Class 4; D000109:Acetylcholine