Phenotypes Associated with This Genotype

Genotype
MGI:6314154

• Allelic Composition: Grn^tm2.1Far/Grn^tm2.1Far
• Genetic Background: involves: 129S4/SvJae * C57BL/6

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

Microgliosis, thalamic neuronal TDP-43+ cytoplasmic inclusions, reduced synaptic density, lipofuscinosis, and skin lesions due to excessive grooming in Grn^tm2.1Far/Grn^tm2.1Far mice

mortality/aging

decreased survivor rate ( J:259651 )

• 30% lower median survival of 575 days compared to 816 days in wild-type mice

premature death ( J:259651 )

• 30% lower median survival of 575 days compared to 816 days in wild-type mice

behavior/neurological

increased grooming behavior ( J:259651 )

• mice exhibit compulsive grooming

hematopoietic system

microgliosis ( J:259651 )

• mice exhibit age-dependent microgliosis

abnormal macrophage physiology ( J:259651 )

• bone marrow-derived macrophages exhibit an exaggerated inflammatory response after treatment with lipopolysaccharide (LPS) and IFN-gamma

immune system

microgliosis ( J:259651 )

• mice exhibit age-dependent microgliosis

abnormal macrophage physiology ( J:259651 )

• bone marrow-derived macrophages exhibit an exaggerated inflammatory response after treatment with lipopolysaccharide (LPS) and IFN-gamma

integument

skin lesions ( J:259651 )

• compulsive grooming leads to development of skin lesions over time

nervous system

microgliosis ( J:259651 )

• mice exhibit age-dependent microgliosis

abnormal thalamus neuron morphology ( J:259651 )

• mice exhibit increased levels of total and phosphorylated TDP-43 in the cytoplasm of thalamic neurons

abnormal synapse morphology ( J:259651 )

• mice exhibit an age-dependent reduction in synapse density

neuronal cytoplasmic inclusions ( J:259651 )

• mice exhibit increased levels of total and phosphorylated TDP-43 in the cytoplasm of thalamic neurons

pigmentation

lipofuscinosis ( J:259651 )

• mice exhibit an increase in levels of lipofuscin in the brain indicating lysosomal dysfunction

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:259651