Deficient LAR expression decreases basal forebrain cholinergic neuronal size and hippocampal cholinergic innervation

Absence of p75NTRCauses Increased Basal Forebrain Cholinergic Neuron Size, Choline Acetyltransferase Activity, and Target Innervation

“…Interestingly, previous quantitative doseresponse studies using sympathetic and dorsal root ganglion sensory neurons derived from p75 N TR null mutant mice demonstrated that NGF had reduced, rather than increased, potency through TrkA in the absence of p75 N TR (Davies et al, 1993;Lee et al, 1994a;Longo et al, 1997). These observations suggest complex, multifaceted p75 N TR functions that may positively or negatively mediate neurotrophic parameters.…”

“…They were generated as follows: p75 N TR Ϫ/Ϫ mice were backcrossed with wild-type mice from one of the parental strains (BAL B/c) to generate heterozygous F1 progeny; these then were inbred via brother-sister mating to produce F2 progeny consisting of all three genotypes. Genotypes were determined by PCR of tail genomic DNA, as previously described (Yeo et al, 1997), using the following primers corresponding to sequences in exon 3 of the mouse p75 N TR gene that is disrupted in the mutant allele and to sequences in the neomycin gene insert: p75 NTR sense/antisense, 5Ј-TGTTACGTTCTCTGACGTG-GTGAG-3Ј/5Ј-TCAGCCCAGGGTGTGCA-C TC -3Ј; neomycin sense/ antisense, 5Ј-CATTCGACCACCAAGCGAAAC -3Ј/5Ј-CAGCAATA-TCACGGGTAGCCAAC -3Ј. A 345 bp product corresponding to the p75 N TR gene was detected in p75 N TR ϩ/ϩ, and a 294 bp product corresponding to the neomycin gene was detected in p75 N TR Ϫ/Ϫ mice; both products were detected in p75 N TR ϩ/Ϫ mice.…”

“…Histolog ical procedures. Histological procedures for ChAT immunoreactivity were performed according to previously described methods (Butcher, 1983;Gould et al, 1991;Yeo et al, 1997). Mice were perf used transcardially with cold (4°C) PBS, followed by 4% paraformaldehyde containing 0.2% picric acid in 0.1 M phosphate buffer.…”

Receptor Tyrosine Phosphatases Guide Vertebrate Motor Axons during Development

“…Experiments using putative dominant-negative mutants of PTP-and PTP-␦ suggest involvement of these RPTPs in pathfinding in vivo (Johnson et al, 2001;Rashid-Doubell et al, 2002). LAR, PTP-␦, and PTP-mutant mice have nervous system phenotypes, some of which may be related to axon growth (Yeo et al, 1997;Elchebly et al, 1999;Wallace et al, 1999;Uetani et al, 2000). Finally, LAR and PTP-null mutants exhibit aberrant peripheral nerve regeneration (Xie et al, 2001;McLean et al, 2002;Thompson et al, 2003;Van der Zee et al, 2003).…”

Overexpression of the LAR (leukocyte antigen-related) protein-tyrosine phosphatase in muscle causes insulin resistance

“…A. J. Hendriks and M. P. H. Møller, personal communication). The absence of LAR in the brain, where it may be important for establishing and maintaining neuronal networks (22,23), might contribute to the complex phenotype seen in LAR knockout mice (21) and obscure a role of LAR in glucose homeostasis. Even if LAR has no role in regulating insulin signaling under normal conditions in vivo, it is possible that overexpressed LAR (as has been observed in insulinresistant states), might pathologically impair insulin signaling.…”