• mice die at E10.5

• shortened

• severe

• at E9.0, mice exhibit increased apoptosis in the pharyngeal mesoderm compared with wild-type mice

• while sensory axons reach the skin only rudimentary sensory axon branching is established within the skin

• mice have 25% of the wild-type number of muscle spindles

• sensory afferents fail to invade the spinal cord and are found in an extreme lateral position at the dorsal root entry zone

• sensory afferents are bifurcated at the entry point

• sensory afferent fibers fail to approach the midline at the distal segments and continue to occupy an extreme lateral position

• unlike wild-type cells, dorsal root ganglia neurons survive in culture without the addition of neurotrophic agents

• whole dorsal root ganglia require neurotrophin-3 for survival

• mice have 25% of the wild-type number of muscle spindles

• mutants exhibit a defect in muscle spindle differentiation in the dorsal root ganglion and motor neurons

• mutants exhibit a defect in muscle spindle differentiation in the dorsal root ganglion and motor neurons

• selective absence of Schwann cells at E16.5 in adductor and gracilis muscles but not in other muscles

• parvalbumin+ proprioceptive afferents are present in E16.5 hindlimb muscles and initiate contact with individual myofibers, but they do not develop annulospiral branches around the myofibers

• parvalbumin+ proprioceptive terminals at muscle spindles remain primitive and unbranched at E18.5

• however, survival and initial differentiation of proprioceptive afferent sensory neurons is not impaired

• large diameter axons in the saphenous nerve become thinner

• many myelinated axons greater than 4 um are lost in the interosseous nerve

• reduced in number and rudimentary

• however, NF200+ axons innervating the dermal papillae are normal

• reduced in number with axonal loss

• remaining corpuscles are small and have irregularly shaped cores

• following skin indentation, mice exhibit prolonged rapid adapting mechanoreceptor (RAM) firing that continues into the beginning of the static phase with increased RAM spiking over a wide range of displacement amplitudes and shortened spike intervals compared with control mice

• following skin indentation, mice exhibit decreased von Frey thresholds of short adapting mechanoreceptors compared with control mice

• mice treated with linopirdine fail to exhibit a decrease in interspike interval in the saphenous nerve unlike control mice

• however, mice exhibit normal short adapting mechanoreceptor, D-hair receptors and Adelta nociceptor firing following skin indentation

• in large diameter but not medium diameter fibers

• innervating Pacinian corpuscles

• the hair in the dorsal hindpaw is shorter than the hair in the back skin and resembles hair of the tail

• mild in adults

• however, mice exhibit normal body weight at P15

• on a rotarod test

• mutants appear normal

• mutants appear normal

• fails to form, on six sides out of eight, in four embryos

• missing, on five sides out of six, in three embryos

• 1 week after birth, few mice are still alive

• mice exhibit abnormal development of facial neuron precursors that do not migrate into r6 unlike in wild-type mice

• mice exhibit impaired development of retrotapezoid nucleus neurons compared with wild-type mice

• the parafacial area e-pF oscillator exhibits only occasional motor activity bursts with reduced frequency compared to in wild-type mice

• rhythmic phrenic discharges are less frequent than in wild-type mice

• mice fail to exhibit an accelerated respiratory-like rhythm phrenic discharge in response to low pH challenge unlike similarly treated wild-type mice

• surviving mice are smaller than wild-type mice

• mice exhibit abnormal development of facial neuron precursors that do not migrate into r6 unlike in wild-type mice

• mice exhibit impaired development of retrotapezoid nucleus neurons compared with wild-type mice

• at E9.5, mice exhibit fewer progenitor cells migration into the outflow tract compared with control mice

• at E13.5 both ventral and dorsal projecting lateral motor column neurons appear stunted or atrophied and in some cases are retracted

• at E13.5 at the forelimb level the number of lateral motor column medial and lateral motor neurons are reduced by about 30% and 25%, respectively; however no difference in the number of lateral motor column lateral motor neurons is detected at E12.5

• at E13.5 at the hindlimb level the number of lateral motor column medial and lateral motor neurons are reduced by about 17% and 20%, respectively

• proprioceptive afferents terminate prematurely in the intrmediate zone of the spinal cord

• mice exhibit a 35% decrease in Lim1+/Islet2+ motor neurons compared to wild-type mice

• overall survival is extended 64 days

• in transgenic mice expressing a motorneuron specific Cre, disease onset is delayed 18 days

• progression from onset through early disease is delayed 31 days

• later disease progression is slowed with an average extension of 15 days