Phenotypes associated with this allele

• Allele Symbol: Cln3^tm1Nbm
• Allele Name: targeted mutation 1, Robert L Nussbaum
• Allele ID: MGI:1933976
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Cln3^tm1Nbm/Cln3^tm1Nbm	129S6/SvEvTac-Cln3^tm1Nbm	MGI:3715473
hm2	Cln3^tm1Nbm/Cln3^tm1Nbm	involves: 129S6/SvEvTac * C57BL/6J	MGI:5788563
hm3	Cln3^tm1Nbm/Cln3^tm1Nbm	involves: 129S6/SvEvTac * NIH Black Swiss	MGI:2175783

Genotype
MGI:3715473

hm1

• Allelic Composition: Cln3^tm1Nbm/Cln3^tm1Nbm
• Genetic Background: 129S6/SvEvTac-Cln3^tm1Nbm

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

vision/eye

abnormal retina morphology ( J:109790 )

• first evidence of storage material at about 10 weeks of age

abnormal retina ganglion layer morphology ( J:109790 )

• early site for accumulation of storage material

abnormal retina inner nuclear layer morphology ( J:109790 )

• early site for accumulation of storage material

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
neuronal ceroid lipofuscinosis 3		DOID:0110731	OMIM:204200	J:109790

Genotype
MGI:5788563

hm2

• Allelic Composition: Cln3^tm1Nbm/Cln3^tm1Nbm
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6J

immune system

abnormal macrophage physiology ( J:233445 )

♂ • mutant bone marrow macrophages exhibit increased adhesiveness to CD11c ligands in vitro

decreased macrophage cytokine production ( J:233445 )

♂ • bone marrow macrophages stimulated with LPS exhibit decreased secretion of IFN-gamma, IL-1beta, IL-17, IL-12p70 and IL-9

abnormal professional antigen presenting cell morphology ( J:233445 )

♂ • increase in surface and total protein levels of CD11c in antigen presenting cells (bone marrow macrophages, bone marrow dendritic cells, and peritoneal macrophages)

♂ • increase in surface levels of CD11c on mononuclear phagocytes (CD14+ monocytes in the blood and F4/80+ macrophages in the spleen)

♂ • decrease in surface levels of CD11b in bone marrow macrophages and dendritic cells and peritoneal macrophages

abnormal dendritic cell physiology ( J:233445 )

♂ • mutant bone marrow dendritic cells exhibit increased adhesiveness to CD11c ligands in vitro

hematopoietic system

abnormal macrophage physiology ( J:233445 )

♂ • mutant bone marrow macrophages exhibit increased adhesiveness to CD11c ligands in vitro

decreased macrophage cytokine production ( J:233445 )

♂ • bone marrow macrophages stimulated with LPS exhibit decreased secretion of IFN-gamma, IL-1beta, IL-17, IL-12p70 and IL-9

cellular

abnormal cell adhesion ( J:233445 )

♂ • mutant bone marrow dendritic cells and bone marrow marcrophages exhibit increased adhesiveness to CD11c ligands in vitro

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
neuronal ceroid lipofuscinosis 3		DOID:0110731	OMIM:204200	J:233445

Genotype
MGI:2175783

hm3

• Allelic Composition: Cln3^tm1Nbm/Cln3^tm1Nbm
• Genetic Background: involves: 129S6/SvEvTac * NIH Black Swiss

nervous system

abnormal brain morphology ( J:58230 )

• marked accumulation of storage material

abnormal brainstem morphology ( J:58230 )

• accumulation of storage material in neuronal cell bodies and glial cells of the reticular formation

abnormal basal ganglion morphology ( J:58230 )

• marked accumulation of storage material in neuronal cell bodies and glial cells

abnormal hippocampus morphology ( J:58230 )

• accumulation of storage material in neuronal cell bodies and glial cells, particularly in interneurons of the hilar formation, stratum oriens, stratum radiatum, and CA1-3

• hypertrophy and reduced numbers of most interneurons

abnormal cerebral cortex morphology ( J:58230 )

• marked accumulation of storage material in neuronal cell bodies and glial cells

• reduced numbers of parvalbumin positive interneurons

cellular

abnormal lysosome morphology ( J:58230 )

• marked accumulation of storage material in neuronal cell bodies in the brain

• first detectable at 3 months of age and increasing to 12 months

• widely distributed throughout the cytoplasm but not the nucleus

• contain mitochondrial ATP synthase subunit c

• found in both neuronal and glial cells

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
neuronal ceroid lipofuscinosis 3		DOID:0110731	OMIM:204200	J:58230