title: Partial rescue of NT-3 null mutant phenotype by a PDGF-β regulated transgene.
abstract: The phenotype of neurotrophin-3 (NT-3) null mutant mice is characterized by sensory ataxia and early postnatal death. Previous analysis revealed a severe depletion of peripheral sensory, sympathetic and parasympathetic neurons. Most of the deficits are established early during embryonic development. Whereas absence of proprioceptive afferents can explain the sensory ataxia, the reasons for early postnatal death are unclear. To circumvent the limitations imposed by early mortality of null mutants we generated mouse line expressing NT-3 transgenes driven by the platelet-derived growth factor β-chain (PDGF-β) promoter, which is known to be active in neurons and mesenchyme derivatives. Mice carrying one or two PDGF-NT3 transgenes on a background null for wildtype NT-3 were generated by crossing with an NT-3 null strain. Although still ataxic, mice from this cross could survive for periods longer than a year. Histological analysis revealed a limited rescue of muscle spindles and parvalbumin immunoreactive sensory neurons.
authors.affiliation: Center for Experimental Medicine, Medical University of Silesia, ul. Medyków 4, 40-752 Katowice, Poland. jbarski-cmd@sum.edu.pl
authors.forename: Jarosław J
authors.initials: JJ
authors.lastname: Barski
authors.forename: Christian
authors.initials: C
authors.lastname: Helbig
authors.forename: Michael
authors.initials: M
authors.lastname: Meyer
mesh_terms: D000818:Animals; D001259:Ataxia / Q000235:genetics* / Q000378:metabolism* / Q000401:mortality; D003433:Crosses, Genetic; D004195:Disease Models, Animal; D005260:Female; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009154:Mutation; D009414:Nerve Growth Factors / Q000172:deficiency* / Q000378:metabolism / Q000502:physiology*; D009421:Nervous System Malformations / Q000235:genetics / Q000378:metabolism / Q000401:mortality; D010641:Phenotype; D020574:Proto-Oncogene Proteins c-sis / Q000235:genetics / Q000502:physiology*; D011897:Random Allocation; D015996:Survival Rate
chemical_list: D009414:Nerve Growth Factors; D020574:Proto-Oncogene Proteins c-sis; C518911:neurotropin 3, mouse