Phenotypes Associated with This Genotype

Genotype
MGI:5444200

• Allelic Composition: Grn^tm1.1Far/Grn^tm1.1Far
• Genetic Background: involves: 129S4/SvJae * C57BL/6J * FVB/N

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

immune system

microgliosis ( J:188324 )

• increased 3-fold in MPTP-treated mice

increased interleukin-1 beta secretion ( J:188324 )

• from microglia exposed to LPS and IFN-gamma

increased interleukin-10 secretion ( J:188324 )

• from microglia exposed to LPS and IFN-gamma

increased interleukin-6 secretion ( J:188324 )

• from microglia exposed to LPS and IFN-gamma

increased tumor necrosis factor secretion ( J:188324 )

• from microglia exposed to LPS and IFN-gamma

vision/eye

abnormal retina ganglion cell morphology ( J:218705 )

• levels of nuclear TDP-43 is reduced in retinal ganglion cell layer neurons of 18 month old mutants, whereas levels of cytoplasmic TDP-43 are unchanged

• depletion of nuclear TDP-43 also occurs in 12 month old mice before significant retinal ganglion cell layer neuron loss

• neither nuclear nor cytoplasmic TDP-43 inclusions are seen in retinal ganglion cell layer neurons

retina ganglion cell degeneration ( J:218705 )

• loss of ganglion cell layer cells in 18 month old mutants

abnormal retina nerve fiber layer morphology ( J:218705 )

• progressive thinning of the retinal nerve fiber layer

decreased a-wave amplitude ( J:218705 )

• age-dependent reduction in a wave amplitude

decreased b-wave amplitude ( J:218705 )

• age-dependent reduction in b wave amplitude

abnormal cone electrophysiology ( J:218705 )

• mutants have reduced amplitudes of photopic negative responses at 18, but not 12, months of age

nervous system

microgliosis ( J:188324 )

• increased 3-fold in MPTP-treated mice

loss of dopaminergic neurons ( J:188324 )

• greater in mice treated with MPTP compared with control mice

abnormal retina ganglion cell morphology ( J:218705 )

• levels of nuclear TDP-43 is reduced in retinal ganglion cell layer neurons of 18 month old mutants, whereas levels of cytoplasmic TDP-43 are unchanged

• depletion of nuclear TDP-43 also occurs in 12 month old mice before significant retinal ganglion cell layer neuron loss

• neither nuclear nor cytoplasmic TDP-43 inclusions are seen in retinal ganglion cell layer neurons

neurodegeneration ( J:218705 )

• retinal neurodegeneration

retina ganglion cell degeneration ( J:218705 )

• loss of ganglion cell layer cells in 18 month old mutants

abnormal neuron physiology ( J:188324 , J:218705 )

• culture media conditioned with microglia exposed to LPS and IFN-gamma can induce increased cell death in wild-type neurons (J:188324)

• primary cortical neurons grown in culture exhibit shorter survival than wild-type neurons (J:218705)

increased susceptibility to dopaminergic neuron neurotoxicity ( J:188324 )

• induced by MPTP

homeostasis/metabolism

increased susceptibility to dopaminergic neuron neurotoxicity ( J:188324 )

• induced by MPTP

cellular

increased susceptibility to dopaminergic neuron neurotoxicity ( J:188324 )

• induced by MPTP

hematopoietic system

microgliosis ( J:188324 )

• increased 3-fold in MPTP-treated mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Grn-related frontotemporal lobar degeneration with Tdp43 inclusions		DOID:0060672	OMIM:607485	J:218705