Mouse Genome Informatics
hm1
    Cptm1Hrs/Cptm1Hrs
involves: 129X1/SvJ * Black Swiss
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype

Increase in storage iron content in Cptm1Hrs/Cptm1Hrs liver and spleen

homeostasis/metabolism
• homozygotes showed elevated serum ferritin
• aceruloplasminemic mice showed normal copper gastrointestinal absorption, hepatic uptake, and biliary copper excretion
• the copper content of brain, heart, spleen, and kidney was normal, and homozygotes exhibited normal copper-zinc superoxide dismutase activity in these tissues
• notably, hepatic copper content was significantly elevated in aceruloplasminemic mice
• ferrokinetic studies showed normal rates of iron absorption, initial tissue iron distribution, and plasma iron turnover
• no differences were detected in cellular iron uptake; however, homozygotes displayed a significant impairment in hepatocyte iron efflux
• at 1 year of age, there was no evidence of diabetes, anemia, or neurological deficits despite iron accumulation in these sites
• progressive accumulation of parenchymal iron, reaching a 3- to 6-fold increase in the iron content of the spleen by 1 year of age
• the spleen displayed normal cellular architecture with abundant iron in reticuloendothelial cells
• progressive accumulation of parenchymal iron, reaching a 3- to 6-fold increase in the iron content of the liver by 1 year of age (J:57730)
• the liver displayed normal cellular architecture with abundant iron in reticuloendothelial cells (J:57730)
• hepatic iron displayed a 3.5-fold increase in aceruloplasminemic mice due to loss of ferroxidase function (J:71807)

hematopoietic system
N
• the hemoglobin concentration remained normal relative to wild-type (J:57730)
• progressive accumulation of parenchymal iron, reaching a 3- to 6-fold increase in the iron content of the spleen by 1 year of age
• the spleen displayed normal cellular architecture with abundant iron in reticuloendothelial cells

liver/biliary system
• aceruloplasminemic mice showed normal copper gastrointestinal absorption, hepatic uptake, and biliary copper excretion
• the copper content of brain, heart, spleen, and kidney was normal, and homozygotes exhibited normal copper-zinc superoxide dismutase activity in these tissues
• notably, hepatic copper content was significantly elevated in aceruloplasminemic mice
• progressive accumulation of parenchymal iron, reaching a 3- to 6-fold increase in the iron content of the liver by 1 year of age (J:57730)
• the liver displayed normal cellular architecture with abundant iron in reticuloendothelial cells (J:57730)
• hepatic iron displayed a 3.5-fold increase in aceruloplasminemic mice due to loss of ferroxidase function (J:71807)

immune system
• progressive accumulation of parenchymal iron, reaching a 3- to 6-fold increase in the iron content of the spleen by 1 year of age
• the spleen displayed normal cellular architecture with abundant iron in reticuloendothelial cells

Mouse Models of Human Disease
OMIM IDRef(s)
Aceruloplasminemia 604290 J:57730 , J:71807


Mouse Genome Informatics
cn2
    Cptm1Hrs/Cptm1Hrs
Hephtm1.1Jdun/Hephtm1.1Jdun
Tg(BEST1-cre)1Jdun/0

involves: 129X1/SvJ * C57BL/6 * C57BL/6NTac
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
vision/eye
• retinal pigment epithelium (RPE) cells exhibit atrophy, hypertrophy and large vacuoles with cells extruded into the photoreceptor layer (J:196540)
• however, PRE cells are not auto-fluorescent (J:196540)

homeostasis/metabolism
• increased iron accumulation in the retinal pigment epithelium at 3 months of age (J:196540)
• increased transferrin receptor levels are decreased in the retinal pigment epithelium and neural retinas indicating increased labile iron levels (J:196540)

pigmentation
• retinal pigment epithelium (RPE) cells exhibit atrophy, hypertrophy and large vacuoles with cells extruded into the photoreceptor layer (J:196540)
• however, PRE cells are not auto-fluorescent (J:196540)


Mouse Genome Informatics
cn3
    Cptm1Hrs/Cptm1Hrs
Hephtm1.1Jdun/Hephtm1.1Jdun
Tg(BEST1-cre)1Jdun/0
Tg(Rho-cre)#Yzl/0

involves: 129X1/SvJ * C57BL/6 * C57BL/6NTac
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
• iron levels in retinal pigment epithelium cells are not increased beyond levels in Cptm1Hrs/Cptm1Hrs Hephtm1.1Itl/ Hephtm1.1Itl Tg(BEST1-cre)1Jdun mice (J:196540)
• bipolar cells exhibit an increase in L-ferritin levels (J:196540)


Mouse Genome Informatics
cn4
    Cptm1Hrs/Cptm1Hrs
Hephtm1.1Jdun/Hephtm1.1Jdun
Tg(Rho-cre)#Yzl/0

involves: 129X1/SvJ * C57BL/6NTac
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
N
• mice exhibit normal retinal pigment epithelium iron levels (J:196540)


Mouse Genome Informatics
cx5
    Cptm1Hrs/Cptm1Hrs
Hephsla/Hephsla

involves: 129X1/SvJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
• increased iron accumulation in the retinal pigment epithelium (J:196540)

vision/eye
• retinal pigment epithelium cells are auto-fluorescent (J:196540)

pigmentation
• retinal pigment epithelium cells are auto-fluorescent (J:196540)


Mouse Genome Informatics
cx6
    Cptm1Hrs/Cptm1Hrs
Hephsla/Y

involves: 129X1/SvJ * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype

Accumulation of of iron in Cptm1Hrs/Cptm1Hrs Hephsla/Y retinal pigment epithelium and photoreceptors

homeostasis/metabolism
• retinas exhibit increased iron at 5-6 months of age, with highest levels in the RPE and photoreceptor outer segments (J:92620)
• levels of the cytosolic iron storage protein ferritin are increased in retinas (J:92620)
• iron accumulation in the retina and ciliary body (J:136925)

vision/eye
• subretinal macrophage infiltration is seen by 9 months of age (J:136925)
• iron accumulation in the nonpigmented ciliary epithelium of the ciliary body at 7 months of age (J:136925)
• levels of ferritin light chain (L-ferritin) are increased in the nonpigmented ciliary epithelium of 7 month old mutants (J:136925)
• retinas exhibit increased iron at 5-6 months of age, with highest levels in the RPE and photoreceptor outer segments (J:92620)
• neurosensory retinas (without the RPE) have higher iron levels at 3 and 6 months of age than wild-type mice (J:136925)
• levels of transferrin receptor are undetectable in the retina except for a thin layer near the junction of photoreceptor inner and outer segments (J:136925)
• levels of isoprostane F2alpha-VI are increased in 6 month old retinas, indicating oxidative stress (J:136925)
• age dependent subretinal neovascularization (J:92620)
(J:136925)
• local photoreceptor degeneration (J:92620)
• age dependent retinal epithelium hypertrophy, hyperplasia and necrosis (J:92620)
• iron accumulation in the retinal pigment epithelium (RPE) in 3 and 6 month old mutants (J:136925)
• accumulation of lipofuscin-like material in the retinal pigment epithelium with age (J:136925)
• retinas of mutants surviving 6-9 months exhibit focal areas of hypopigmentation in the midperipheral retina (J:92620)
• age dependent retinal epithelium hyperplasia (J:92620)
(J:136925)
• mutants surviving 6-9 months exhibit retinal degeneration (J:92620)
• age-dependent retinal degeneration with neovascularization that is first visible at 7 months of age; degeneration consists of RPE hyperplasia, RPE hypertrophy, and focal photoreceptor degeneration characterized by thinning of the ONL, inner segment vacuolization, and loss of outer segments (J:136925)
• by 12-13 months of age, hypertrophic RPE cells are seen in 90% of the total retinal length, loss of inner and outer segments, thinning of the ONL, and subretinal macrophage infiltration, focal areas of neovascularization (J:136925)
• choroidal thinning (J:92620)
• 9-month old mutants show activated complement in Bruch's membrane (J:136925)

cardiovascular system
• age dependent subretinal neovascularization (J:92620)
(J:136925)

nervous system
• local photoreceptor degeneration (J:92620)

pigmentation
• age dependent retinal epithelium hypertrophy, hyperplasia and necrosis (J:92620)
• iron accumulation in the retinal pigment epithelium (RPE) in 3 and 6 month old mutants (J:136925)
• accumulation of lipofuscin-like material in the retinal pigment epithelium with age (J:136925)
• retinas of mutants surviving 6-9 months exhibit focal areas of hypopigmentation in the midperipheral retina (J:92620)
• age dependent retinal epithelium hyperplasia (J:92620)
(J:136925)

immune system
• subretinal macrophage infiltration is seen by 9 months of age (J:136925)


Mouse Genome Informatics
cx7
    Cptm1Hrs/Cptm1Hrs
Hephtm1.2Jdun/Hephtm1.2Jdun

involves: 129X1/SvJ * C57BL/6 * C57BL/6NTac
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
hematopoietic system
(J:196540)

homeostasis/metabolism
• increased iron accumulation in the neural retina, retinal pigment epithelium cells and the choroid (J:196540)

nervous system
• neurodegenerative symptoms as in Cptm1Hrs Hephsla double homozygotes (J:196540)