Phenotypes associated with this allele

• Allele Symbol: Fgf14^tm1Dor
• Allele Name: targeted mutation 1, David M Ornitz
• Allele ID: MGI:2183403
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Fgf14^tm1Dor/Fgf14^tm1Dor	129S6/SvEvTac-Fgf14^tm1Dor	MGI:3663128
hm2	Fgf14^tm1Dor/Fgf14^tm1Dor	B6.129S6-Fgf14^tm1Dor	MGI:3663129
hm3	Fgf14^tm1Dor/Fgf14^tm1Dor	involves: 129S6/SvEvTac * C57BL/6	MGI:3768548
cx4	Fgf12^tm1Gol/Fgf12^tm1Gol Fgf14^tm1Dor/Fgf14^tm1Dor	involves: 129S1/Sv * 129S6/SvEvTac * 129X1/SvJ * C57BL/6	MGI:3768547

Genotype
MGI:3663128

hm1

• Allelic Composition: Fgf14^tm1Dor/Fgf14^tm1Dor
• Genetic Background: 129S6/SvEvTac-Fgf14^tm1Dor

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

growth/size/body

slow postnatal weight gain ( J:77806 )

• Background Sensitivity: growth lags behind controls during the 3rd and 4th weeks of life but parallels growth in controls at all other times

behavior/neurological

increased susceptibility to pharmacologically induced seizures ( J:77806 )

abnormal motor capabilities/coordination/movement ( J:77806 )

• nonepileptic forelimb clonic spasms and hyperextension of hindlimbs - paroxysmal dyskinesia

limb grasping ( J:77806 )

• retract hind feet and clench digits when suspended by the tail

ataxia ( J:77806 )

• ataxic gait

impaired balance ( J:77806 )

• poor performance on both a ledge and a platform test

impaired coordination ( J:77806 )

• poor performance on an accelerating rotarod test and no improvement with practice

decreased grip strength ( J:77806 )

• inferior ability to climb on an inclined screen

• inability to stay on in an inverted screen test

abnormal posture ( J:77806 )

• widened stance

abnormal locomotor activation ( J:77806 )

• slow to initiate movement although overall activity levels are normal

abnormal gait ( J:77806 )

• shuffling footprint pattern

nervous system

abnormal nervous system physiology ( J:77806 )

• hyperactive response to cocaine, amphetamine, and specific dopamine receptor agonists is reduced

• impaired dopamine 2 receptor-mediated signalling

• both the striatonigral and striatopallial nerve pathways function abnormally although the striatopallial pathway is affected more

increased susceptibility to pharmacologically induced seizures ( J:77806 )

Genotype
MGI:3663129

hm2

• Allelic Composition: Fgf14^tm1Dor/Fgf14^tm1Dor
• Genetic Background: B6.129S6-Fgf14^tm1Dor

growth/size/body

decreased body weight ( J:77806 )

• Background Sensitivity: growth of mice on a B6 background is normal through weaning although adult weight is 15% smaller than controls

behavior/neurological

increased susceptibility to pharmacologically induced seizures ( J:77806 )

impaired spatial learning ( J:134733 )

♂ • mice exhibit impaired acquisition performance during place trials in both escape path length and latency to find the submerged platform

♂ • mice also show impaired acquisition performance when they are restested in the water maze and required to learn another submerged platform location in the presence of different spatial cues

♂ • increasing the memory load for the water navigation task results in performance deficits in mice that are not seen with less challenging memory demands

♂ • however, mice exhibit normal conditioned fear and passive avoidance performance

abnormal motor capabilities/coordination/movement ( J:77806 )

• nonepileptic forelimb clonic spasms and hyperextension of hindlimbs - paroxysmal dyskinesia

limb grasping ( J:77806 )

• retract hind feet and clench digits when suspended by the tail

ataxia ( J:77806 , J:134733 )

• ataxic gait (J:77806)

♂ (J:134733)

impaired balance ( J:77806 )

• poor performance on both a ledge and a platform test

impaired coordination ( J:77806 , J:134733 )

• poor performance on an accelerating rotarod test and no improvement with practice (J:77806)

♂ • mice exhibit impaired performance on the platform and inverted screen and on the constant speed and accelerating rotarod (J:134733)

decreased grip strength ( J:77806 , J:134733 )

• inferior ability to climb on an inclined screen (J:77806)

• inability to stay on in an inverted screen test (J:77806)

♂ • mice show reduced forelimb strength in gripping a bar (J:134733)

abnormal posture ( J:77806 )

• widened stance

abnormal locomotor activation ( J:77806 )

• slow to initiate movement although overall activity levels are normal

abnormal gait ( J:77806 )

• shuffling footprint pattern

increased locomotor activity ( J:134733 )

♂ • mice are hyperactive, showing more ambulations than wild-type mice during a 1 hour test period

nervous system

abnormal nervous system physiology ( J:77806 )

• hyperactive response to cocaine, amphetamine, and specific dopamine receptor agonists is reduced

• impaired dopamine 2 receptor-mediated signalling

• both the striatonigral and striatopallial nerve pathways function abnormally although the striatopallial pathway is affected more

increased susceptibility to pharmacologically induced seizures ( J:77806 )

reduced long-term potentiation ( J:134733 )

♂ • mice exhibit impaired theta burst induced LTP

♂ • however, mice show normal hippocampus, parahippocampal region and amygdala anatomy

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
spinocerebellar ataxia type 27		DOID:0050976	OMIM:193003	J:134733

Genotype
MGI:3768548

hm3

• Allelic Composition: Fgf14^tm1Dor/Fgf14^tm1Dor
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6

behavior/neurological

decreased grip strength ( J:128732 )

• mice exhibit grip weakness when tested on an inverted grid and show shortened ledge retention time compared to wild-type mice

weakness ( J:128732 )

nervous system

abnormal nervous system electrophysiology ( J:144561 )

• most Purkinje neurons lack spontaneous and tonic firing

• however, individual action potential waveforms in Purkinje cells and evoked excitatory postsynaptic currents (EPSCs) in Purkinje neurons are similar to wild-type mice

abnormal CNS synaptic transmission ( J:128732 )

• granule neuron excitability is impaired

Genotype
MGI:3768547

cx4

• Allelic Composition: Fgf12^tm1Gol/Fgf12^tm1Gol; Fgf14^tm1Dor/Fgf14^tm1Dor
• Genetic Background: involves: 129S1/Sv * 129S6/SvEvTac * 129X1/SvJ * C57BL/6

behavior/neurological

abnormal response to new environment ( J:128732 )

• mice exhibit increased activity when placed in a new environment

ataxia ( J:128732 )

• severe

decreased grip strength ( J:128732 )

• mice fall off a grid when titled at a 45 degree angle and do not pull a rod with any measurable force when pulled backwards by their tails

weakness ( J:128732 )

abnormal gait ( J:128732 )

hyperactivity ( J:128732 )

• mice exhibit increased activity when disturbed or placed in a new environment

nervous system

abnormal CNS synaptic transmission ( J:128732 )

• granule neuron excitability is more severely impaired than in Fgf14^tm1Dor mice (1 firing compared to 2 in Fgf14^tm1Dor mice)

abnormal channel response ( J:128732 )

• sodium channel inactivation parameters are altered in cerebellar granule neurons