Phenotypes associated with this allele

• Allele Symbol: Clu^tm1Jakh
• Allele Name: targeted mutation 1, Judith A K Harmony
• Allele ID: MGI:2181011
• Summary: 5 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Clu^tm1Jakh/Clu^tm1Jakh	involves: 129S2/SvPas	MGI:3784304
hm2	Clu^tm1Jakh/Clu^tm1Jakh	involves: 129S2/SvPas * Black Swiss	MGI:5432925
hm3	Clu^tm1Jakh/Clu^tm1Jakh	involves: Black Swiss * FVB/N	MGI:2663412
cx4	Apoe^tm1Unc/Apoe^tm1Unc Clu^tm1Jakh/Clu^tm1Jakh Tg(APPV717F)109Ili/Tg(APPV717F)109Ili	involves: 129P2/OlaHsd * 129S2/SvPas	MGI:3721541
cx5	Clu^tm1Jakh/Clu^tm1Jakh Tg(APPV717F)109Ili/Tg(APPV717F)109Ili	involves: 129S2/SvPas	MGI:3721530

Genotype
MGI:3784304

hm1

• Allelic Composition: Clu^tm1Jakh/Clu^tm1Jakh
• Genetic Background: involves: 129S2/SvPas

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

nervous system

nervous system phenotype ( J:58019 )

N • astrocytes secrete a normal composition of lipid particles

Genotype
MGI:5432925

hm2

• Allelic Composition: Clu^tm1Jakh/Clu^tm1Jakh
• Genetic Background: involves: 129S2/SvPas * Black Swiss

renal/urinary system

renal/urinary system phenotype ( J:74983 )

N • mice exhibit no evidence of tubulointerstitial disease, vascular lesions, inflammatory infiltrates, necrosis, or amyloid deposits, regardless of the extent of glomerulopathy

N • glomerular basement membranes are normal and lack discernible deposits

abnormal glomerular capillary morphology ( J:74983 )

• collapse of capillary lumens at 21 months of age

hematuria ( J:74983 )

• an occasional mutant develops hematuria

abnormal glomerular mesangium morphology ( J:74983 )

• up to 75% of glomeruli exhibit moderate to severe mesangial lesions at 21 months of age

increased mesangial cell number ( J:74983 )

• mesangial hypercellularity noted in 6-mo-old mice that have undergone unilateral nephrectomy at 3 months and are then fed a high-protein diet

abnormal mesangial matrix morphology ( J:74983 )

• electron-dense tubulo-fibrillar structures arranged in parallel arrays are detected in the mesangial matrix at 21 months, consistent with immune complex deposits

• more electron-dense deposits found in 6-mo-old mice that have undergone unilateral nephrectomy at 3 months and are then fed a high-protein diet

expanded mesangial matrix ( J:74983 )

• variable mesangial expansion observed at 21 months, but not at 6 months, of age

• more severe mesangial expansion noted in 6-mo-old mice that have undergone unilateral nephrectomy at 3 months and are then fed a high-protein diet

cortical renal glomerulopathies ( J:74983 )

• at 21 months of age, mice display progressive mesangial expansion, collapse of capillary lumens, and deposition of collagen and immune complexes, unlike wild-type and heterozygous controls

renal glomerular protein deposits ( J:74983 )

• immune complexes of IgG, IgM, IgA, and in some cases C1q, C3, and C9 are detected in the mesangium at 21 months of age

• increased deposition of C1q and C3 in 6-mo-old mice that have undergone unilateral nephrectomy at 3 months and are then fed a high-protein diet

renal glomerular immunoglobulin deposits ( J:74983 )

• immune complexes of IgG, IgM and IgA are noted as early as 4 weeks of age

renal glomerulus fibrosis ( J:74983 )

• accumulation of collagen deposits in the glomeruli

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:74983 )

N • mice display no signs of proteinuria or any alterations in serum and urine proteins relative to controls

hematuria ( J:74983 )

• an occasional mutant develops hematuria

cardiovascular system

abnormal glomerular capillary morphology ( J:74983 )

• collapse of capillary lumens at 21 months of age

cellular

increased mesangial cell number ( J:74983 )

• mesangial hypercellularity noted in 6-mo-old mice that have undergone unilateral nephrectomy at 3 months and are then fed a high-protein diet

Genotype
MGI:2663412

hm3

• Allelic Composition: Clu^tm1Jakh/Clu^tm1Jakh
• Genetic Background: involves: Black Swiss * FVB/N

cardiovascular system

abnormal heart morphology ( J:65660 )

• after immunization with cardiac myosin, mutant hearts become pale and enlarged, mutants exhibit 3-fold greater heart tissue injury than wild-type

abnormal myocardium layer morphology ( J:65660 )

• 21 days after myocarditis initiation, mice show significant cardiac tissue injury than wild-type mice

abnormal myocardial fiber morphology ( J:65660 )

• after immunization, myocyte necrosis is observed in some animals

decreased myocardial fiber number ( J:65660 )

• 7 weeks following myocarditis, widespread loss of myocardial fibers is found in mutant hearts, whereas none is seen in wild-type controls

abnormal heart ventricle morphology ( J:65660 )

• ventricular damage in females is 6-fold greater than in wild-type females; males do not show as severe cardiac damage

decreased cardiac muscle contractility ( J:65660 )

• postmyocarditis heart function is impaired with decreased shortening fraction measured in mutants;

heart inflammation ( J:65660 )

• severe, diffuse inflammation with large inflammatory aggregates occurs after immunization with cardiac myosin

myocarditis ( J:65660 )

• severe myocarditis after immunization with cardiac myosin, more severe than in wild-type

muscle

abnormal myocardium layer morphology ( J:65660 )

• 21 days after myocarditis initiation, mice show significant cardiac tissue injury than wild-type mice

abnormal myocardial fiber morphology ( J:65660 )

• after immunization, myocyte necrosis is observed in some animals

decreased myocardial fiber number ( J:65660 )

• 7 weeks following myocarditis, widespread loss of myocardial fibers is found in mutant hearts, whereas none is seen in wild-type controls

decreased cardiac muscle contractility ( J:65660 )

• postmyocarditis heart function is impaired with decreased shortening fraction measured in mutants;

immune system

heart inflammation ( J:65660 )

• severe, diffuse inflammation with large inflammatory aggregates occurs after immunization with cardiac myosin

myocarditis ( J:65660 )

• severe myocarditis after immunization with cardiac myosin, more severe than in wild-type

homeostasis/metabolism

cardiac edema ( J:65660 )

• immunized mice show cardiac edema

Genotype
MGI:3721541

cx4

• Allelic Composition: Apoe^tm1Unc/Apoe^tm1Unc; Clu^tm1Jakh/Clu^tm1Jakh; Tg(APPV717F)109Ili/Tg(APPV717F)109Ili
• Genetic Background: involves: 129P2/OlaHsd * 129S2/SvPas

nervous system

amyloid beta deposits ( J:107702 )

• at 6 months of age, most mice have substantial amyloid beta (Abeta) deposits

• by 12 months of age, mice have more amyloid beta (Abeta) deposits in the hippocampus and cortex than other genotypes

• Abeta deposits are more numerous and fill all parts of hippocampus and some of the cortex by 12 months; abundant compact and diffuse plaques are observed

• mice have greater levels of thioflavine-S-positive (fibrillar) Abeta deposits than other genotypes, similar to transgenic homozygotes with normal Apoe and Clu

increased cerebrospinal fluid amyloid beta 40 isoform level ( J:107702 )

• at 3 months, cerebrospinal fluid levels of Abeta₄₀ are elevated; Abeta₄₀ increase is greater than in transgenic, single Apoe-null mice

increased cerebrospinal fluid amyloid beta 42 isoform level ( J:107702 )

• at 3 months, cerebrospinal fluid levels of Abeta₄₂ are elevated

homeostasis/metabolism

amyloidosis ( J:107702 )

• mice have significant amyloid burden, greater than shown by other genotypes

• at 12 months, mice have highest tissue levels of soluble Abeta₄₀ and Abeta₄₂, with high levels of insoluble Abeta₄₂

• at 3 months, mice have higher levels of carbonate soluble Abeta₄₀ and Abeta₄₂ compared to other genotypes

amyloid beta deposits ( J:107702 )

• at 6 months of age, most mice have substantial amyloid beta (Abeta) deposits

• by 12 months of age, mice have more amyloid beta (Abeta) deposits in the hippocampus and cortex than other genotypes

• Abeta deposits are more numerous and fill all parts of hippocampus and some of the cortex by 12 months; abundant compact and diffuse plaques are observed

• mice have greater levels of thioflavine-S-positive (fibrillar) Abeta deposits than other genotypes, similar to transgenic homozygotes with normal Apoe and Clu

increased cerebrospinal fluid amyloid beta 40 isoform level ( J:107702 )

• at 3 months, cerebrospinal fluid levels of Abeta₄₀ are elevated; Abeta₄₀ increase is greater than in transgenic, single Apoe-null mice

increased cerebrospinal fluid amyloid beta 42 isoform level ( J:107702 )

• at 3 months, cerebrospinal fluid levels of Abeta₄₂ are elevated

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Alzheimer's disease		DOID:10652		J:107702

Genotype
MGI:3721530

cx5

• Allelic Composition: Clu^tm1Jakh/Clu^tm1Jakh; Tg(APPV717F)109Ili/Tg(APPV717F)109Ili
• Genetic Background: involves: 129S2/SvPas

nervous system

amyloid beta deposits ( J:78357 , J:107702 )

• by 12 months of age, ~60% of mice show amyloid beta (Abeta) deposition (J:78357)

• decreased percentage of Abeta-immunoreactive deposits that are thioflavine-S-positive (2.46 vs 19.4% thioflavine load/Abeta load) compared to Clu-sufficient mice (J:78357)

• many Abeta deposits have few or no detectable dystrophic neurites around them (J:78357)

• by 12 months of age, mice have amyloid beta (Abeta) deposits in the hippocampus and cortex (J:107702)

abnormal neurite morphology ( J:78357 )

• a 10-fold reduction in dystrophic neurites in hippocampi at 12 months compared to Clu-sufficient transgenic mice and a 5-fold reduction in number of dystrophic neurites per amyloid deposit

homeostasis/metabolism

amyloidosis ( J:78357 )

• only 20% of mice have thioflavine-S-positive (fibrillar Abeta or amyloid) deposits in the cortex at 12 months

• mice have lower hippocampal amyloid burden (0.89%) at 12 months than Clu-sufficient transgenic mice; amyloid load increases to 2.25% by 15 months

amyloid beta deposits ( J:78357 , J:107702 )

• by 12 months of age, ~60% of mice show amyloid beta (Abeta) deposition (J:78357)

• decreased percentage of Abeta-immunoreactive deposits that are thioflavine-S-positive (2.46 vs 19.4% thioflavine load/Abeta load) compared to Clu-sufficient mice (J:78357)

• many Abeta deposits have few or no detectable dystrophic neurites around them (J:78357)

• by 12 months of age, mice have amyloid beta (Abeta) deposits in the hippocampus and cortex (J:107702)

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Alzheimer's disease		DOID:10652		J:78357