Phenotypes associated with this allele

• Allele Symbol: Ntrk2^tm1Bbd
• Allele Name: targeted mutation 1, Mariano Barbacid
• Allele ID: MGI:1857814
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Ntrk2^tm1Bbd/Ntrk2^tm1Bbd	involves: 129S2/SvPas	MGI:3612894
hm2	Ntrk2^tm1Bbd/Ntrk2^tm1Bbd	involves: 129S2/SvPas * C57BL/6	MGI:2175187
ht3	Ntrk2^tm1Bbd/Ntrk2^tm1Kln	involves: 129S1/Sv * 129S2/SvPas * 129X1/SvJ	MGI:3708465
cn4	Ntrk2^tm1Bbd/Ntrk2^tm2Kln Tg(Camk2a-cre)159Kln/0	involves: 129S2/SvPas * CBA/J	MGI:2448690

Genotype
MGI:3612894

hm1

• Allelic Composition: Ntrk2^tm1Bbd/Ntrk2^tm1Bbd
• Genetic Background: involves: 129S2/SvPas

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

mortality/aging

postnatal lethality, complete penetrance ( J:104489 )

• average lifespan is 4.48 days (all survive past the first day), however those that survive past 5 days, die at an average age of 15.5 days and the maximum life span is 21 days

nervous system

abnormal cerebellum development ( J:49472 )

• defects in cerebellar development, with the intercrural, prepyramidal, and uvular fissures shallower at P12

abnormal barrel cortex morphology ( J:103935 )

• delay in barrel formation through P6, but the deficiency disappears by P8

abnormal Purkinje cell dendrite morphology ( J:49472 )

• dendritic trees of Purkinje cells are reduced by 22% in length

abnormal somatic nervous system morphology ( J:104489 )

abnormal sensory neuron innervation pattern ( J:103935 , J:104489 )

• innervation into layer IV of the cortex by thalamic axons is uniform (rather than segregated into individual barrels) and exhibits a reduced branching within this layer compared to controls at P6, but becomes less apparent by P8 (J:103935)

• severe loss of radial fibers in the apical region of the cochlea that becomes less severe toward the base (J:104489)

small cochlear ganglion ( J:104489 )

• 13% reduction of neuron number in cochlear ganglia

small geniculate ganglion ( J:104489 )

• 95% reduction of neuron number in geniculate ganglia

small petrosal ganglion ( J:104489 )

• 66% reduction of neuron number in nodose/petrosal ganglia

small trigeminal ganglion ( J:104489 )

• 27% reduction of neuron number in trigeminal ganglia

small nodose ganglion ( J:49472 , J:104489 )

• 87% of nodose neurons are lost by P0 (J:49472)

• 66% reduction of neuron number in nodose/petrosal ganglia (J:104489)

small vestibular ganglion ( J:49472 , J:104489 )

• 60% of vestibular neurons are lost by birth (J:49472)

• 83% reduction of neuron number in vestibular ganglia (J:104489)

small L4 dorsal root ganglion ( J:104489 )

• 27% reduction of neuron number in L4 dorsal root ganglia

Genotype
MGI:2175187

hm2

• Allelic Composition: Ntrk2^tm1Bbd/Ntrk2^tm1Bbd
• Genetic Background: involves: 129S2/SvPas * C57BL/6

mortality/aging

neonatal lethality, incomplete penetrance ( J:56847 )

• most die by P1, although a few survive into the first week

behavior/neurological

absent suckling reflex ( J:56847 )

• do not orient toward a stimulus (stroking under the chin) and do not open mouth except for an occasional gasp

no swallowing reflex ( J:56847 )

• homozygotes inhale milk instead of swallowing it when manually fed

abnormal vibrissae reflex ( J:56847 )

• unresponsive to tactile stimuli in vibrissae area

nervous system

small facial motor nucleus ( J:56847 )

• up to 70% reduction in density of facial motor nucleus

abnormal sensory neuron innervation pattern ( J:29245 )

• at P1, homozygotes display deficient innervation in the vestibular and cochlear sensory epithelia

• at E16.5, some vestibular and cochlear fibres initially reach their peripheral targets but fail to maintain innervation and thus degenerate

abnormal cochlear OHC afferent innervation pattern ( J:29245 )

• at P1, homozygotes fail to innervate the OHCs of the cochlea

• the sensory epithelium containing OHCs is generally devoid of nerve fibers, although retracting neurites with residual synaptic contacts are occasionally detected

• in contrast, the innervation pattern of IHCs appears normal

abnormal inner ear vestibular sensory neuron innervation pattern ( J:29245 )

• in the utricular macula nerve fibers have reached the base of the hair cells, but are degenerating and retracting from their targets

• no innervation is observed in the sensory epithelia of the ampullary cristae

decreased motor neuron number ( J:56847 )

• reduction in motor neuron number in lumbar region only (L2-L5)

abnormal cochlear ganglion morphology ( J:29245 )

• at P1, cochlear ganglia display areas of reduced cell density and large extracellular spaces, albeit to a lesser extent than vestibular ganglia

small cochlear ganglion ( J:29245 )

• at P1, a 11% and 15% reduction in cochlear ganglion size and neuron number is, respectively, observed

• small-sized type II neurons (innervating OHCs) are preferentially lost (77% reduction), whereas larged-sized type I neurons (innervating IHCs) remain unaffected

• no significant changes in cochlear ganglion size or neuron number are noted at E14.5 or E18.5

small trigeminal ganglion ( J:56847 )

• about 40% reduction in the number of ganglion neurons, with the largest decrease in the anterior half of the ganglion, however size of neurons is normal

abnormal vestibular ganglion morphology ( J:29245 )

• at P1, vestibular ganglia display areas of reduced cell density and large extracellular spaces

• at this stage, cells with nuclei surrounded by a very small amount of cytoplasm are abundant

small vestibular ganglion ( J:29245 )

• at E18.5, a 38% reduction in vestibular neuron number is observed

• by P1, a 57% reduction in vestibular ganglion size and neuron number is observed

• however, no significant changes in vestibular ganglion size or neuron number are noted at E14.5

abnormal vestibular nerve morphology ( J:29245 )

• at P1, vestibular nerves lack membrane vesicles and contain residual synaptic plates at their nerve endings; degenerating nerve fibers, empty perineural sheets and lack of myelination are observed

small dorsal root ganglion ( J:56847 )

• about 30% reduction in the number of neurons in the dorsal root ganglia from thoracic level 12 to the lumbar level 3 regions of the spinal cord

hearing/vestibular/ear

abnormal cochlear OHC afferent innervation pattern ( J:29245 )

• at P1, homozygotes fail to innervate the OHCs of the cochlea

• the sensory epithelium containing OHCs is generally devoid of nerve fibers, although retracting neurites with residual synaptic contacts are occasionally detected

• in contrast, the innervation pattern of IHCs appears normal

abnormal crista ampullaris neuroepithelium morphology ( J:29245 )

• at P1, no innervation is observed in the sensory epithelia of the ampullary cristae

abnormal inner ear vestibular sensory neuron innervation pattern ( J:29245 )

• in the utricular macula nerve fibers have reached the base of the hair cells, but are degenerating and retracting from their targets

• no innervation is observed in the sensory epithelia of the ampullary cristae

abnormal utricular macula morphology ( J:29245 )

• at P1, nerve fibers have reached the base of hair cells in the utricular maculae but appear to degenerate and retract from their targets

Genotype
MGI:3708465

ht3

• Allelic Composition: Ntrk2^tm1Bbd/Ntrk2^tm1Kln
• Genetic Background: involves: 129S1/Sv * 129S2/SvPas * 129X1/SvJ

mortality/aging

mortality/aging ( J:84871 )

N • life span is normal

hearing/vestibular/ear

abnormal cochlear sensory epithelium morphology ( J:84871 )

• lack of type II nerve cells in cochlear sensory epithelium at the level of the outer hair cells

abnormal cochlear OHC afferent innervation pattern ( J:84871 )

• type II afferent fibers lacking a t birth and first post natal week in the medial and apical turns of the cochlea but they are present in the basal turn

• in adults, the pattern is reversed

abnormal type I vestibular cell ( J:84871 )

• failure of calyx like structures at the ends of afferent neurons to enclose hair cells

• innervation defects most severe in the ampullary cristae

abnormal inner ear vestibular sensory neuron innervation pattern ( J:84871 )

• defects in both afferent and efferent innervation of the vestibular sensory epithelium

increased or absent distortion product otoacoustic emission threshold ( J:84871 )

• hearing thresholds are elevated at all frequencies in heterozygotes

nervous system

abnormal cochlear OHC afferent innervation pattern ( J:84871 )

• type II afferent fibers lacking a t birth and first post natal week in the medial and apical turns of the cochlea but they are present in the basal turn

• in adults, the pattern is reversed

abnormal type I vestibular cell ( J:84871 )

• failure of calyx like structures at the ends of afferent neurons to enclose hair cells

• innervation defects most severe in the ampullary cristae

abnormal inner ear vestibular sensory neuron innervation pattern ( J:84871 )

• defects in both afferent and efferent innervation of the vestibular sensory epithelium

Genotype
MGI:2448690

cn4

• Allelic Composition: Ntrk2^tm1Bbd/Ntrk2^tm2Kln; Tg(Camk2a-cre)159Kln/0
• Genetic Background: involves: 129S2/SvPas * CBA/J

behavior/neurological

abnormal learning/memory/conditioning ( J:58229 )

• a certain degree of task-specific long-term memory appears to be present but mutants show increasingly impaired learning behavior or inappropriate coping response when facing complex and/or stressful learning paradigms such as in contextual fear conditioning, two-way avoidance, radial maze and water maze learning

abnormal avoidance learning behavior ( J:58229 )

• in avoidance learning, mutants first react normally to the new environment but fall into a persisting maladaptive locomotor activity

abnormal contextual conditioning behavior ( J:58229 )

• in the contextual fear conditioning, mutants fail to develop an appropriate freezing response after 30 min but show correct freezing after 24 hours yet not following exposure to tone

abnormal spatial learning ( J:58229 )

• mutants show impaired spatial learning in the Morris water maze test and partial impairment in the eight-arm radial maze

increased thigmotaxis ( J:58229 )

• mutants exhibit persistent thigmotaxis in the water maze

nervous system

abnormal myelination ( J:58229 )

• the number of myelinated axons in the CA1 region of the hippocampus is reduced by 23%

reduced long-term potentiation ( J:58229 )

• reduction in LTP at CA1 hippocampal synapses