Phenotypes associated with this allele

• Allele Symbol: Klc1^tm1Gsn
• Allele Name: targeted mutation 1, Lawrence S B Goldstein
• Allele ID: MGI:2136259
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Klc1^tm1Gsn/Klc1^tm1Gsn	B6.129-Klc1^tm1Gsn	MGI:4429145
hm2	Klc1^tm1Gsn/Klc1^tm1Gsn	either: (involves: 129S/SvEv * 129S1/Sv * 129X1/SvJ) or (involves: 129S1/Sv * 129X1/SvJ * C57BL/6)	MGI:3582994
hm3	Klc1^tm1Gsn/Klc1^tm1Gsn	involves: 129S1/Sv * 129X1/SvJ	MGI:4949219
cx4	Klc1^tm1Gsn/Klc1^+ Tg(APP695)3Dbo/?	involves: 129S1/Sv * 129X1/SvJ * C3H/HeJ * C57BL/6	MGI:3582996

Genotype
MGI:4429145

hm1

• Allelic Composition: Klc1^tm1Gsn/Klc1^tm1Gsn
• Genetic Background: B6.129-Klc1^tm1Gsn

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

nervous system

abnormal brain white matter morphology ( J:148380 )

• reduction of white matter is observed in corpus callosum

tau protein deposits ( J:148380 )

• phosphorylated tau deposits are observed in ventral axons along roots of the spinal cord, however, no abnormal accumulations are observed in neuronal cell bodies

• soluble levels of total and phosphorylated tau are increased in brainstem and spinal cord, and insoluble tau forms are increased in spinal cord, however, overall levels are similar to wild-type

abnormal axon morphology ( J:148380 )

• proximal axonal swelling is visible in cervical spinal cord, swelling is progressive and age-dependent

• axonal swelling observed in ventral roots of spinal cord

• the number of large caliber axons are reduced in peripheral motor roots

• swollen and distended axons with disrupted microtubule networks, anomalous tubuloreticular structures and atypical accumulations of membrane stacks are observed in hippocampal neurons

abnormal spinal cord white matter morphology ( J:148380 )

• reduction of white matter is observed in the cervical spinal cord

axon degeneration ( J:148380 )

• degeneration is observed in the corpus callosum, anterior commissure of the brain in 18 month old mice

axonal dystrophy ( J:148380 )

• giant axonal enlargements are observed proximal to motor neuron cell bodies in ventral spinal cord

• giant dystrophies have massive neurofilament accumulation with intermingled vesicles

abnormal axonal transport ( J:148380 )

• polarized neurons transiently transfected with a YFP-APP fusion exhibit a decrease in the proportion of amyloid precursor protein (APP) vesicles moving in the anterograde direction, an increase in retrograde vesicles and a reduction in net velocity and average run length for anterograde and retrograde vesicles

• phosphorylated neurofilaments are increased in the dentate gyrus and CA1 region in 18 month old mice

Genotype
MGI:3582994

hm2

• Allelic Composition: Klc1^tm1Gsn/Klc1^tm1Gsn
• Genetic Background: either: (involves: 129S/SvEv * 129S1/Sv * 129X1/SvJ) or (involves: 129S1/Sv * 129X1/SvJ * C57BL/6)

growth/size/body

decreased body size ( J:57877 )

• significantly smaller than normal

behavior/neurological

impaired coordination ( J:57877 )

• reduced ability to hang upside down from chicken wire

Genotype
MGI:4949219

hm3

• Allelic Composition: Klc1^tm1Gsn/Klc1^tm1Gsn
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

cellular

abnormal vesicle-mediated transport ( J:170887 )

• neurons exhibit impaired anterograde and retrograde vesicle transport compared with wild-type cells

Genotype
MGI:3582996

cx4

• Allelic Composition: Klc1^tm1Gsn/Klc1⁺; Tg(APP695)3Dbo/?
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C3H/HeJ * C57BL/6

nervous system

amyloid beta deposits ( J:96346 )

• levels of amyloid beta are consistently elevated relative to controls

abnormal axon morphology ( J:96346 )

• increased axonal swelling independent of amyloid deposition

homeostasis/metabolism

amyloid beta deposits ( J:96346 )

• levels of amyloid beta are consistently elevated relative to controls

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Alzheimer's disease		DOID:10652		J:96346