Targeted deletion of all isoforms of the trkC gene suggests the use of alternate receptors by its ligand neurotrophin-3 in neuronal development and implicates trkC in normal cardiogenesis

Abstract

We have generated null mutant mice that lack expression of all isoforms encoded by the trkC locus. These mice display a behavioral phenotype characterized by a loss of proprioceptive neurons. Neuronal counts of sensory ganglia in the trkC mutant mice reveal less severe losses than those in NT-3 null mutant mice, strongly suggesting that NT-3, in vivo, may signal through receptors other than trkC. Mice lacking either NT-3 or all trkC receptor isoforms die in the early postnatal period. Histological examination of trkCdeficient mice reveals severe cardiac defects such as atrial and ventricular septal defects, and valvular defects including pulmonic stenosis. Formation of these structures during development is dependent on cardiac neural crest function. The similarities in cardiac defects observed in the trkC and NT-3 null mutant mice indicate that the trkC receptor mediates most NT-3 effects on the cardiac neural crest.

Dependence receptors: a new paradigm in cell signaling and cancer therapy

“…Similarly, inactivation of either TrkB or brain-derived neurotrophic factor results in an equivalent loss of mechanoceptive neurons (Ernfors et al, 1994;Minichiello et al, 1995). On the other hand, neonates invalidated for TrkC present a loss of 30% DRG neurons, whereas NT-3 À/À neonates have lost 70% of them (Tessarollo et al, 1994(Tessarollo et al, , 1997. This is in agreement with the view that TrkC, contrary to TrkA and B, can trigger, when deprived of ligand, an active apoptotic signaling.…”

Mouse Ror2 receptor tyrosine kinase is required for the heart development and limb formation

“…First, mRor2 is required for cardiac septal formation. Recent genetic analyses have revealed that many regulatory molecules, including growth factors, receptors and transcription factors, are involved in the development of the heart (Nagasawa et al 1996;Basson et al 1997;Li et al 1997;Tessarollo et al 1997;de la Pompa et al 1998;Ranger et al 1998;Schott et al 1998;Tachibana et al 1998; reviewed in Burn & Goodship 1996;Lyons 1996;Rossant 1996;Barinaga 1998), although in general their roles are not restricted to septal formation. Interestingly, defects of the cardiac septum have been, thus far, the major abnormality observed in the cardio-vascular system of mRor2 À/À mice.…”

Neurotrophin‐3 signaling in mammalian Merkel cell development

“…So far, the reason for the discrepancy between our work and the report by Cronk et al (2002) remains elusive. The TrkC null mouse line (Tessarollo et al, 1997), the stage of development, and the location in which Merkel cell differentiation was monitored, the whisker follicle, were the same in both studies. One difference lies in the Merkel cell markers that have been used.…”

“…TrkC heterozygous mice (Tessarollo et al, 1997) were maintained on a C57BL/6 inbred background. Homozygous mutant mice do not express any TrkC protein (Tessarollo et al, 1997).…”

“…Homozygous mutant mice do not express any TrkC protein (Tessarollo et al, 1997). Four-week-old timedpregnant females were obtained by superovulation according to Hogan et al (1994).…”