| 14365 | Q61086 | FZD3_MOUSE | Frizzled-3 (Fz-3) (mFz3) | DISRUPTION PHENOTYPE | Neonate knockout mice have a curly tail, flexed lower limbs, breathe irregularly and typically die within 30 min of birth. Central nervous system (CNS) shows severe defects in the development of several major axon tracts, including: a nearly complete absence of the three early most prominent axon tracts in the brain and the ventral branch of the trigeminal nerve, absence of subcortical and striatal axons, the anterior commissure, misrouting of thalamocortical axons, a nearly complete absence of the corticospinal tract, the fasciculus retroflexus, and the mammillothalamic tract, poor fasciculation of the medial lemniscus and a disorganization of axon bundles in the reticular formation, severe defect in the asymmetric rostrocaudal orientation of dopaminergic and serotonergic axons, a large reduction or complete absence of ascending spinal axon tracts in the braistem, midbrain and thalamus, peripheral nerves defect in several motor neurons, such as in the VIIth and XIIth cranial motor nerves, the phrenic nerve, and the spinal motor nerve which failed to form connections with their respective targets and display also aberrant migration of a subpopulation of cranial neural crest cells (PubMed:12351730, PubMed:24347548, PubMed:24799694). Neonate knockout mice show fewer S-phase proliferating neuroblasts, premature cell cycle exit and enhanced apoptosis in early-stage superior cervical ganglia (SCGs), and in some cases, complete absence of sympathetic innervation of several peripheral targets (PubMed:21325504). Display also impaired rostral turning by growth cones of spinal cord commissural sensory axons (PubMed:14671310). FZD3 and FZD6 double knockout embryos have a curled tail, exhibit defects in neural tube and eyelids closure, in the orientation of hair bundles on inner-ear sensory cells and die at birth (PubMed:16495441). The following conditional knockout mice display the corresponding phenotypes: dopaminergic neuron-specific shows a defect in the orientation and growth of midbrain dopaminergic axons with an absence of striatum innervation; retinal ganglion cell (RGC)-specific displays a misrouting of a subset of optic tract axons and a lack of the medial terminal nucleus (MTN) innervation; neocortex neuron-specific displays a total absence of the posterior part of the anterior commissure and aberrant axon trajectories appearing in the external capsule; ventral telencephalon neuron-specific shows corticothalamic, thalamocortical and corticospinal tracts defect to various extent; telencephalon neuron-specific exhibits the full spectrum of axon defects seen in the classical null mutant knockout mice; cholinergic neuron-specific shows an absence of cholinergic fiber tracts passing through the striatum, a defective caudal migration of neurons of the VIIth motor nucleus and a loss of motor innervation to the face, a decrease in motor innervation of the tongue by the XIIth nerve and a complete loss of cholinergic neurons in the vomeronasal organ; oligodendrocyte neuron-specific leads to the complete spectrum of motor neuron phenotypes shown by the classical mutant knockout mice; caudal and upper thorax region-specific leads to a loss of motor innervation and an atrophy of anterior compartment muscles in the lower hindlimb by the deep peroneal nerve and a nearly absence in ascending spinal sensory axons in the brainstem, midbrain and thalamus altering the ability to transmit sensory information from the trunk and limbs to the brain in postnatal life (PubMed:24347548, PubMed:24799694). {ECO:0000269|PubMed:12351730, ECO:0000269|PubMed:14671310, ECO:0000269|PubMed:16495441, ECO:0000269|PubMed:21325504, ECO:0000269|PubMed:24347548, ECO:0000269|PubMed:24799694}. |