Mouse Genome Informatics
hm1
    Ldlrtm1Her/Ldlrtm1Her
B6.129S7-Ldlrtm1Her
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype

Adiposity in Ldlrtm1Her/Ldlrtm1Her and Scd1ab-2J/Scd1ab-2J Ldlrtm1Her/Ldlrtm1Her mice

homeostasis/metabolism
• streptozotocin (STZ) treatment leads to 3-fold higher level of blood glucose in mice fed a high fat diet (J:100916)
• these high glucose levels persist for at least 12 weeks after STZ treatment (J:100916)
• when fed a western style diet for 12 weeks (J:130278)
• when fed a western style diet for 12 weeks
• streptozotocin (STZ) induced diabetes leads to blood cholesterol levels that are twice those of non-diabetic mice 6 weeks post-induction and three times greater 8 weeks post- induction (J:100916)
• when fed a western style diet for 12 weeks, male mice exhibit a higher circulating cholesterol level than in Ldlrtm1Her Scd1ab-2J homozygotes (J:130278)
• when fed a high-cholesterol diet, NMR proton spectra of lipids indicates a level of photon intensity for HDL of 0.77 compared to 0.83 in wild-type mice
• mice develop severe cholesterolemia when receiving a high fat diet from 6 to 30 weeks (elevated levels are detected at 6, 15, and 30 weeks) (J:61287)
• seen at 3-4 months of age (J:72027)
• 10 fold increase in total cholesterol on a high fat diet compared to a 150% increase for controls (J:137264)
• 3 fold cholesterol elevation on a normal diet relative to controls (J:137264)
• slightly elevated at 3 and 8 months of age
• when fed a high cholesterol diet, NMR proton spectra of lipids indicates a level of photon intensity for LDL of 0.88 compared to 0.84 in wild-type mice (J:130794)
• compared to in Ldlrtm1Her Scd1ab-2J homozygotes when fed a western style diet for 12 weeks (J:130278)
• when fed a high cholesterol diet, NMR proton spectra of lipids indicates a level of photon intensity for VLDL of 0.92 compared to 0.88 in wild-type mice (J:130794)
• when fed a western style diet for 12 weeks
• livers exhibit slightly, but significantly, higher levels of cholesterol
• seen at 3-4 months of age (J:72027)
• when fed a western style diet for 12 weeks, female mice exhibit a higher circulating triglyceride level than in Ldlrtm1Her Scd1ab-2J homozygotes (J:130278)
• elevated on a high fat diet (J:137264)
• compared to in Ldlrtm1Her Scd1ab-2J homozygotes when fed a western style diet for 12 weeks
• when fed a western style diet for 12 weeks, mice exhibit a 5-fold higher hepatic triglyceride level than in Ldlrtm1Her Scd1ab-2J homozygotes
• increased amyloid beta 40 but not amyloid beta 42 on a high fat diet

adipose tissue
• when fed a western style diet for 12 weeks
• increased when fed a western style diet for 12 weeks

growth/size
• when fed a western style diet for 12 weeks
• lower body weight on a low cholesterol diet than controls on any diet
• when fed a western style diet for 12 weeks

cardiovascular system
• high-fat diet leads to atherosclerosis (J:100916)
• STZ-induced diabetes leads to an almost 3-fold greater size in total lesion area in the aorta compared to non-diabetic Ldlr tm1Her homozyogotes (J:100916)
• 4 weeks on the Western diet mice have lesions of small fatty streaks on the aorta (J:110061)
• after 12 weeks on a high cholesterol diet, mice exhibit extensive intimal thickening and 60% to 80% of the aortic surface is sudanophilic unlike in wild-type mice (J:130794)
• after 12 weeks on a high cholesterol diet, mice exhibit endothelial disruption and an accumulation of macrophage and foam cells at the site of atherosclerotic plaques (J:130794)

immune system
• increased number of microglia in the hippocampus

liver/biliary system
• livers exhibit slightly, but significantly, higher levels of cholesterol
• when fed a western style diet for 12 weeks, mice exhibit a 5-fold higher hepatic triglyceride level than in Ldlrtm1Her Scd1ab-2J homozygotes
• when fed a western style diet for 12 weeks

behavior/neurological
• take longer to reach the target site in a Morris water maze when fed a high cholesterol diet
• deficient performance in a water radial arm maze regardless of the diet
• perform better than controls on a hanging bar test
• travel greater distances and spend more time in motion in an open field test

nervous system
• increased amyloid beta 40 but not amyloid beta 42 on a high fat diet
• increased number of microglia in the hippocampus
• increased numbers of reactive astrocytes
• further increase in reactive astrocytes on a high fat diet

hematopoietic system
• increased number of microglia in the hippocampus


Mouse Genome Informatics
hm2
    Ldlrtm1Her/Ldlrtm1Her
B6.129S7-Ldlrtm1Her/J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
N
• mice fed a Western diet exhibit normal HDL cholesterol (J:149005)
• when fed regular chow or a high fat diet for 16 weeks, serum triglyceride levels are decreased compared to similarly treated Apoa1tm1Unc Ldlrtm1Her homozygotes
• when fed a Western diet
• when fed a high fat diet, mice exhibit an increase in cholesterol content in the adrenal gland
• whether are fed a high fat diet or regular chow, plasma cholesterol levels are increased relative to similarly treated Apoa1tm1Unc Ldlrtm1Her homozygotes (J:85174)
• when fed a high fat diet, mice exhibit a greater increase in VLDL and LDL (6-fold) compared to Ldlrtm1Her homozygotes (3-fold) (J:85174)
• 15 fold higher on a normal diet than controls (J:104609)
• 40 fold higher than controls on a high fat diet (J:104609)
• when fed regular chow or a high fat diet for 16 weeks, serum HDL levels are increased compared to similarly treated Apoa1tm1Unc Ldlrtm1Her homozygotes
• when fed a high fat diet, mice exhibit a greater increase in VLDL and LDL (6-fold) compared to Ldlrtm1Her homozygotes (3-fold) (J:85174)
• when fed a Western diet compared to Ldlrtm1Her homozygotes fed regular chow (J:149005)
• when fed a high fat diet, mice exhibit a greater increase in VLDL and LDL (6-fold) compared to Ldlrtm1Her homozygotes (3-fold) (J:85174)
• when fed a Western diet (J:149005)
• when fed a high fat diet, mice exhibit a greater increase in liver cholesterol content (11-fold) compared to in similarly treated Apoa1tm1Unc Ldlrtm1Her homozygotes (2.5-fold)

liver/biliary system
• when fed a high fat diet, mice exhibit a greater increase in liver cholesterol content (11-fold) compared to in similarly treated Apoa1tm1Unc Ldlrtm1Her homozygotes (2.5-fold)
• when fed a high fat diet, mice exhibit larger diameter and more frequent lipid droplets than in Apoa1tm1Unc Ldlrtm1Her homozygotes
• LDL updake is decreased by about 2X

endocrine/exocrine glands
• when fed a high fat diet, mice exhibit an increase in cholesterol content in the adrenal gland

cardiovascular system
• after 8 or 20 weeks on a cholesterol diet aortic lesion size is increased compared to mice that are homozygous for both Ldlrtm1Her and Ifngtm1Ts

integument
• when fed a high fat diet
• when fed a high fat diet
• when fed a high fat diet


Mouse Genome Informatics
hm3
    Ldlrtm1Her/Ldlrtm1Her
involves: 129P2/OlaHsd * 129S7/SvEvBrd * C57BL/6 * DBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
• increase in APOB-100
• the HDL phospholipid fraction contains less 16:0 and 18:0 species and is enriched for 20:4 and 22:6 species compared to Apoetm1Unc single mutants
• plasma cholesterol is nearly equal distribution between the HDL and LDL fractions
• increase in the APOB lipoprotein cholesterol level compared to wild-type controls
• there is a 2.3 fold decrease in the ratio of saturated + monounsaturated/polyunsaturated cholesterol ester fatty acid species compared to Apoetm1Unc single mutants
• the ratio of saturated + monounsaturated/polyunsaturated cholesterol ester fatty acid species in the LDL fraction is significantly decreased compared to Apoetm1Unc single mutants


Mouse Genome Informatics
hm4
    Ldlrtm1Her/Ldlrtm1Her
involves: 129S6/SvEvTac * 129S7/SvEvBrd * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype

Phenotype of aortic arch atherosclerotic lesions in Tbx21tm1Glm/Tbx21tm1Glm Ldlrtm1Her/Ldlrtm1Her and Ldlrtm1Her/Ldlrtm1Her mice

cardiovascular system
• atherosclerosis in both aortic arch and descending aorta

homeostasis/metabolism


Mouse Genome Informatics
hm5
    Ldlrtm1Her/Ldlrtm1Her
involves: 129S7/SvEvBrd
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
• circulating VLDL/LDL cholesterol levels are increased compared to in Apobec1tm1Chan homozygotes and wild-type mice
• LDL clearance is slowed
• when fed a chow diet or Western-type diet for 2 and 4 weeks, mice exhibit increased serum cholesterol levels compared to in Apobec1tm1Chan homozygotes and wild-type mice (J:48202)
• plasma cholesterol level is 196mg/dl on a normal diet (J:84694)
• on a chow diet, plasma LDL levels were higher than both those of wild-type mice and Ldlrap1tm1Her homozygous mutant mice (J:84694)
• plasma LDL levels become further elevated on high cholesterol diets (J:84694)
• male mice have a marked increase in plasma LDL cholesterol compared to wild-type (J:114949)
• in wild-type mice parabiosed with Ldlr-null mice (resulting in shared circulation), plasma total cholesterol levels did not increase significantly over pre-surgery levels (J:114949)
• plasma levels are increased 2.5 fold relative to controls (J:169834)
• when fed a chow diet or a Western-type diet for 2 and 4 weeks, mice exhibit increased serum triglyceride levels compared to in Apobec1tm1Chan homozygotes and wild-type mice

Mouse Models of Human Disease
OMIM IDRef(s)
Hypercholesterolemia, Familial 143890 J:84694


Mouse Genome Informatics
hm6
    Ldlrtm1Her/Ldlrtm1Her
involves: 129S7/SvEvBrd * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
growth/size
• mice fed a diabetogenic high fat diet (35.5% carbohydrate and 36.6% fat) (DD diet) or a a diabetogenic high fat diet (35.5% carbohydrate and 36.6% fat) with 0.15% added cholesterol (DDC diet) exhibit weight gain leading to obesity; similar weight gain is seen regardless of diet

homeostasis/metabolism
• mothers on a high fat diet have reduced plasma concentrations of phenylalanine, lysine, valine, isoleucine, and leucine
• levels of other amino acids are normal
• levels in response to ACTH are significantly reduced
• similar levels of hypercholesterolemia are seen in mice fed the DD diet and those fed the DDC diet
• clearance of 125I-LDL from circulation is retarded, uptake of DiI-LDL by hepatocytes is decreased, and uptake of 3H-CE-LDL by the liver is lower compared to wild-type
• circulating fatty free acids are increased in mice fed the DD or the DDC diet, however levels are higher in the mice on the DDC diet
• similar levels of hypertriglyceridemia are seen in mice fed the DD diet and those fed the DDC diet
• ALT levels are increased in mice fed the DD diet and even more so in those fed the DDC diet
• increased fasting glucose levels after dexamethasone treatment
• after dexamethasone treatment
• glucose levels increase during a glucose tolerance test
• 30 minute insulin levels elevated
• less likely to become hypoglycemic during an insulin tolerance test
• hepatic cholesterol levels are increased only in the mice fed the DDC diet
• hepatic triglyceride levels are increased in mice fed the DD or the DDC diet, but higher in those on the DDC diet

nervous system
• on a Western diet, even small arterioles have associated microglia, sometimes within the basal lamina
• 2X as many arterioles have microglia
• reduced cell proliferation in the hippocampus
• reduced density of synaptophysin-immunoreactive presynaptic boutons in the CA1 of the hippocampus (J:120389)
• normal density of synaptophysin-immunoreactive presynaptic boutons in the dentate gyrus (J:120389)
• 32% of the cholesterol in the synaptic plasma membrane is in the exofacial leaflet as compared to 15% for controls
• cholesterol levels in the cytofacial leaflet are reduced
• cholesterol/phospholipid ratio in the synaptic plasma membrane is elevated
• fluidity of both the exofacial leaflet and the cytofacial leaflet of the synaptic plasma membrane are increased relative to controls

cardiovascular system
• wall thickness of brain arterioles having a lumen diameter of 15-40 um is greater than controls
• wall thickness increases on a Western diet
• wall thickness is directly related to the number of associated microglia
• thickened endothelial basal lamina
• reduced number of fenestrations
• narrowing of lumina

behavior/neurological
• mice on a Western diet fail to show improved performance over time in a Morris water maze test (J:116493)
• somewhat slower swimming speed in the acquisition phase of a Morris water maze test (J:120389)
• less time spent in the target quadrant during a probe test (J:120389)
• mice fed a Western diet and tested in a T-maze demonstrate reduced alternation returning more frequently to the blind arm of the maze (J:116493)

vision/eye
• thickened endothelial basal lamina
• reduced number of fenestrations
• narrowing of lumina
• decreased and irregular height
• basal membrane infoldings are less regular
• numerous vacuoles in cytoplasm
• thickened (up to 0.8um on a high fat diet)
• enhanced condensation of collagenous and elastic fibers
• laminations disrupted and large vacuoles become diffusely distributed

other phenotype
• poor survival of pups from mothers on a high fat diet
• intrauterine growth restriction of pups from mothers on a high fat diet
• also reduced birth weight persisting to at least 90 days of age
• offspring with lower gonadal fat pad to body weight ratio
• offspring with larger atherosclerotic lesions

hematopoietic system
• on a Western diet, even small arterioles have associated microglia, sometimes within the basal lamina
• 2X as many arterioles have microglia

immune system
• on a Western diet, even small arterioles have associated microglia, sometimes within the basal lamina
• 2X as many arterioles have microglia
• inflammatory cell foci is seen to a greater extend in the livers of mice fed the DDC diet than the DD diet

pigmentation
• decreased and irregular height
• basal membrane infoldings are less regular
• numerous vacuoles in cytoplasm

cellular
• DD diet fed mice show some apoptotic cells in the liver while those on the DDC diet have a larger increase
• mice on the DDC diet exhibit an increase in hepatic oxidative stress

liver/biliary system
• DD diet fed mice show some apoptotic cells in the liver while those on the DDC diet have a larger increase
• hepatic cholesterol levels are increased only in the mice fed the DDC diet
• hepatic triglyceride levels are increased in mice fed the DD or the DDC diet, but higher in those on the DDC diet
• inflammatory cell foci is seen to a greater extend in the livers of mice fed the DDC diet than the DD diet
• mice on the DD diet and on the DDC diet exhibit higher liver weights than regular chow-fed mice
• mice fed the DD diet exhibit diffuse macrovesicular steatosis with limited inflammation and fibrosis in the liver
• mice fed the DDC diet exhibit both macrovesicular and microvesicular steatosis in the liver
• intrasinusoidal and pericellular fibrosis is seen to a greater extend in the livers of mice fed the DDC diet than the DD diet


Mouse Genome Informatics
hm7
    Ldlrtm1Her/Ldlrtm1Her
involves: 129S7/SvEvBrd * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
• total cholesterol greatly elevated


Mouse Genome Informatics
ht8
    Ldlrtm1Her/Ldlr+
B6.129S7-Ldlrtm1Her
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
• seen at 3-4 months of age
• seen at 3-4 months of age


Mouse Genome Informatics
ht9
    Ldlrtm1Her/Ldlr+
involves: 129S7/SvEvBrd * C57BL/6 * DBA/2
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
• streptozotocin (STZ) treatment leads to 3-fold higher level of blood glucose in mice fed a high fat diet
• these high glucose levels persist for at least 12 weeks after STZ treatment


Mouse Genome Informatics
cn10
    Apoetm1Lmh/Apoetm1Lmh
Ldlrtm1Her/Ldlrtm1Her
Lrp1tm2Her/Lrp1tm2Her
Lyz2tm1(cre)Ifo/Lyz2+

involves: 129P2/OlaHsd * 129S7/SvEvBrd
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cardiovascular system
• the total macrophage and collagen lesion contents are increased
• the percentage (normalized for lesion size) of collagen in lesions is increased; however, the percentages of macrophages and smooth muscle cells in the lesions are similar
• total atherosclerotic lesion area and the proportion of advanced lesions are significantly increased compared to mutant mice expressing Lrp1


Mouse Genome Informatics
cn11
    Ldlrtm1Her/Ldlrtm1Her
Lrp1tm2Her/Lrp1tm2Her
Lyz2tm1(cre)Ifo/Lyz2+

involves: 129P2/OlaHsd * 129S7/SvEvBrd
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• impaired ability to internalize targets coated with LRP ligands
• however, phagocytosis of apoptotic cells in serum free conditions is similar to controls

hematopoietic system
• impaired ability to internalize targets coated with LRP ligands
• however, phagocytosis of apoptotic cells in serum free conditions is similar to controls


Mouse Genome Informatics
cn12
    Ldlrtm1Her/Ldlrtm1Her
Lrp1tm2Her/Lrp1tm2Her
Lyz2tm1(cre)Ifo/Lyz2+

involves: 129P2/OlaHsd * 129S7/SvEvBrd * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• significant decrease in the number of activated glial cells in ischemic tissue after transient middle cerebral artery occlusion
• significant decrease in the number of activated glial cells in ischemic tissue after transient middle cerebral artery occlusion
• significant reduction in the accumulation of nitrotyrosine in the ischemic tissue
• treatment with PLAT fails to restore nitrotyrosine accumulation unlike in mice null for Plat
• 24 hours after transient middle cerebral artery occlusion

homeostasis/metabolism
• significant decrease in the number of activated glial cells in ischemic tissue after transient middle cerebral artery occlusion
• significant reduction in the accumulation of nitrotyrosine in the ischemic tissue
• treatment with PLAT fails to restore nitrotyrosine accumulation unlike in mice null for Plat
• 24 hours after transient middle cerebral artery occlusion

immune system
• significant decrease in the number of activated glial cells in ischemic tissue after transient middle cerebral artery occlusion

hematopoietic system
• significant decrease in the number of activated glial cells in ischemic tissue after transient middle cerebral artery occlusion


Mouse Genome Informatics
cn13
    Ldlrtm1Her/Ldlrtm1Her
Nr1h3tm1.1Djm/Nr1h3tm1.1Djm
Tg(Alb-cre)21Mgn/0

involves: 129S/SvEv * 129S7/SvEvBrd * C57BL/6 * DBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype

Atherosclerosis lesion area is increased in Ldlrtm1Her/Ldlrtm1Her Nr1h3tm1.1Djm/Nr1h3tm1.1Djm Tg(Alb-cre)21Mgn/0 mice and TO901317 treatment reduces these lesions

homeostasis/metabolism
• by 4 weeks in mice fed a western diet
• mice fed a western diet and treated with T0901317 (an Lxr/Nr1h3 agonist) exhibit impaired reverse cholesterol transport compared with control mice
• by 4 weeks in mice fed a western diet
• in mice fed a western diet at the conclusion of the experiment
• mice fed a western diet and treated with T0901317 (an Lxr/Nr1h3 agonist) fail to exhibit a change in plasma lipid levels or an increase in fecal excretion of macrophage-derived sterols but an increase in hepatic sterols compared with control mice
• however, treatment with T0901317 reduces atherosclerosis as in controls

liver/biliary system
• in mice fed a western diet at the conclusion of the experiment

cardiovascular system
• mice fed a western diet exhibit increase in lesion size as detected by macrophage staining compared with control mice
• however, collagen staining or lesions is normal and treatment with T0901317 reduces atherosclerosis as in controls


Mouse Genome Informatics
cn14
    Ldlrtm1Her/Ldlrtm1Her
Lrp1tm2Her/Lrp1tm2Her

involves: 129S7/SvEvBrd
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
• after adenoviral cre infection
• after adenoviral cre infection, concentrations of apoB48 are dramatically increased
• this increase is primarily responsible for the increase in plasma cholesterol and triglyceride levels
• slightly increased after adenoviral cre infection
• after adenoviral cre infection, the total cholesterol profile is dramatically changed
• increase in total plasma cholesterol levels after adenoviral cre infection
• large increase of plasma lipoproteins in the LDL size range after adenoviral cre infection
• large increase of plasma lipoproteins in the chylomicron remnant/VLDL size range after adenoviral cre infection


Mouse Genome Informatics
cn15
    Agtr1atm1Uky/Agtr1atm1Uky
Ldlrtm1Her/Ldlrtm1Her
Tg(Tek-cre)12Flv/0

involves: 129S7/SvEvBrd * C3H * C57BL/6 * C57BL/6N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cardiovascular system
• angiotensin II-treated mice fed a high-fat diet exhibit decreased elastin breaks compared with similarly treated Ldlrtm1Her homozygotes
• angiotensin II-treated mice fed a high-fat diet exhibit decreased medial thickness compared with similarly treated Ldlrtm1Her homozygotes
• angiotensin II-treated mice fed a high-fat diet exhibit less ascending aorta lengthening compared with similarly treated Ldlrtm1Her homozygotes
• angiotensin II-treated mice fed a high-fat diet exhibit less ascending aorta ulcers compared with similarly treated Ldlrtm1Her homozygotes


Mouse Genome Informatics
cn16
    Agtr1atm1Uky/Agtr1atm1Uky
Ldlrtm1Her/Ldlrtm1Her
Tg(Tagln-cre)1Her/0

involves: 129S7/SvEvBrd * C57BL/6 * C57BL/6N * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cardiovascular system
N
• mice fed a high-fat diet exhibit the same amount of angiotensin-induced expansion of ascending aortas and aneurysms as in similarly treated Ldlrtm1Her homozygotes (J:170230)


Mouse Genome Informatics
cn17
    Ldlrtm1Her/Ldlrtm1Her
Lrp1tm2Her/Lrp1tm2Her
Vldlrtm1Her/Vldlrtm1Her
Tg(Mx1-cre)29-4Her/0

involves: 129S7/SvEvBrd * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
• mice show significantly elevated FVIII (Factor 8), similar to Ldlr/Lrp double mutants


Mouse Genome Informatics
cn18
    Ldlrtm1Her/Ldlrtm1Her
Lrp1tm2Her/Lrp1tm2Her
Tg(Mx1-cre)29-4Her/0

involves: 129S7/SvEvBrd * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
• levels are significantly increased (>10-fold) compared to controls
• levels are significantly increased (>10-fold) compared to controls
• mice show significantly elevated FVIII (Factor 8) and VWF (von Willebrand factor) levels, by 4.2- and 3.3-fold respectively


Mouse Genome Informatics
cn19
    Apoetm1Lmh/Apoetm1Lmh
Ldlrtm1Her/Ldlrtm1Her
Lrp1tm2Her/Lrp1tm2Her
Tg(Mx1-cre)29-4Her/0

involves: 129S7/SvEvBrd * C57BL/6J * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
• following pIpC treatment, plasma cholesterol level is lower compared to mutant mice wild-type for Lrp1
• following pIpC treatment, plasma LDL cholesterol level is lower compared to mutant mice wild-type for Lrp1
• following pIpC treatment, plasma VLDL cholesterol level is lower compared to mutant mice wild-type for Lrp1
• following pIpC treatment, plasma triglyceride level is lower compared to mutant mice wild-type for Lrp1
• increase in Factor VIII, von Willebrand factor, and tissue type plasminogen activator levels by 4 weeks after pIpC treatment (J:90547)
• mice show elevated FVIII (Factor 8) levels (J:117317)
• following pIpC treatment, plasma lipoprotein lipase level is higher compared to mutant mice wild-type for Lrp1
• however, no increase in lipoprotein lipase activity is detected

cardiovascular system
• increase in lesion size in pIpC treated mice compared to untreated controls
• however, no change in lesion composition is detected


Mouse Genome Informatics
cn20
    Ldlrtm1Her/Ldlrtm1Her
Lrp1tm2Her/Lrp1tm2Her
Tg(Mx1-cre)29-4Her/0

involves: 129S7/SvEvBrd * C57BL/6J * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
• increase in total plasma cholesterol levels within 10 days of pIpC injection
• large increase of plasma lipoproteins in the LDL size range within 10 days of pIpC injection
• large increase of plasma lipoproteins in the chylomicron remnant/VLDL size range within 10 days of pIpC injection
• within 10 days of pIpC injection
• within 10 days of pIpC injection, concentrations of apoB48 are dramatically increased
• this increase is primarily responsible for the increase in plasma cholesterol and triglyceride levels


Mouse Genome Informatics
cn21
    Ldlrtm1Her/Ldlrtm1Her
Lrp1tm2Her/Lrp1tm2Her
Tg(Tagln-cre)1Her/0

involves: 129S7/SvEvBrd * C57BL/6J * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cardiovascular system
• progressive thickening of the aorta wall with age
• thickening is primarily caused by increased smooth muscle cell proliferation
• aortas are consistently distended and dilated
• pronounced atherosclerosis is seen in the aorta
• on a high cholesterol diet
• addition of Gleevec to the diet protects against atherosclerotic lesion formation
• almost complete occlusion of the mesenteric arteries
• increase in vascular smooth muscle cell proliferation

homeostasis/metabolism
N
• no changes in cholesterol or triglyceride levels are detected compared to mice homozygous for Ldlrtm1Her alone (J:82871)

muscle
• increase in vascular smooth muscle cell proliferation


Mouse Genome Informatics
cx22
    Apobec1tm1Ddsn/Apobec1tm1Ddsn
Ldlrtm1Her/Ldlrtm1Her

B6.129-Apobec1tm1Ddsn Ldlrtm1Her
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
• cholesterol is primarily in the LDL fraction as opposed to controls where it is predominantly in the HDL fraction
• shortened prothrombin times and activated thromboplastin times
• elevated thrombin and antithrombin levels

cardiovascular system
• plaque surface area increases from 24 to 72 weeks of age
• plaques composed of a fibrous cap over a foam cell core
• multilayered smooth muscle cell regions associated with collagen deposition at 24 weeks
• smooth muscle cell numbers diminished after 36 weeks
• collagen throughout the plaque core at 48 weeks


Mouse Genome Informatics
cx23
    Apobec1tm1Ddsn/Apobec1tm1Ddsn
Fggtm1Fjc/Fggtm1Fjc
Ldlrtm1Her/Ldlrtm1Her

B6.129-Fggtm1Fjc Apobec1tm1Ddsn Ldlrtm1Her
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• display better survival to 3 weeks than do mice only deficient for Fgg

homeostasis/metabolism
• cholesterol is primarily in the LDL fraction as opposed to controls where it is predominantly in the HDL fraction
• thrombin and antithrombin levels very highly elevated

cardiovascular system
• plaque surface area increases beyond what is seen in double homozygotes lacking fibrinogen gamma chain deficiency
• fibrous cap thinner than is seen in double homozygotes lacking fibrinogen gamma chain deficiency
• collagen deposition in plaques develops more rapidly than in double homozygotes lacking fibrinogen gamma chain deficiency


Mouse Genome Informatics
cx24
    Agtr1atm1Unc/Agtr1atm1Unc
Ldlrtm1Her/Ldlrtm1Her

B6.129-Ldlrtm1Her Agtr1atm1Unc
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cardiovascular system
• angiotensin II-treated mice fed a high-fat diet do not exhibit ascending aortic aneurysms unlike similarly treated Ldlrtm1Her homozygotes
• bone marrow transplant do not alter incidence of angiotensin II-induced ascending aortic aneurysms compared with similarly treated Ldlrtm1Her homozygotes


Mouse Genome Informatics
cx25
    Apoa1tm1Unc/Apoa1tm1Unc
Ldlrtm1Her/Ldlrtm1Her

B6.129-Ldlrtm1Her Apoa1tm1Unc
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
• when fed regular chow or a high fat diet for 16 weeks, serum triglyceride levels are increased compared to similarly treated Ldlrtm1Her homozygotes
• when fed a high fat diet, female mice exhibit a decrease in aortic cholesterol compared to similarly treated Ldlrtm1Her homozygotes
• however, aortic cholesterol levels in male mice fed a high fat diet are equivalent to in similarly treated Ldlrtm1Her homozygotes and female mice die before completion of the study
• when fed a high fat diet, mice exhibit a decrease in cholesterol content, specifically esterified cholesterol, in the adrenal gland compared to similarly treated Ldlrtm1Her homozygotes
• when mice are fed a high fat diet or regular chow, plasma cholesterol levels are decreased relative to similarly treated Ldlrtm1Her homozygotes
• unlike male Ldlrtm1Her homozygotes, plasma cholesterol levels fail to increased from weeks 8 to 16 on a high fat diet
• when fed a high fat diet, free cholesterol levels fail to increase as much as in similarly treated Ldlrtm1Her homozygotes
• unlike Ldlrtm1Her homozygotes, free cholesterol levels fail to increased from weeks 8 to 16 on a high fat diet
• when mice are fed a high fat diet or regular chow, esterified cholesterol levels are decreased relative to similarly treated Ldlrtm1Her homozygotes
• unlike male Ldlrtm1Her homozygotes, esterified cholesterol levels fail to increased from weeks 8 to 16 on a high fat diet
• when fed a high fat diet, mice exhibit a lesser increase in VLDL and LDL (3-fold) compared to Ldlrtm1Her homozygotes (6-fold)
• when fed regular chow or a high fat diet for 16 weeks, serum HDL levels are decreased compared to similarly treated Ldlrtm1Her homozygotes
• when fed a high fat diet, mice exhibit a lesser increase in VLDL and LDL (3-fold) compared to Ldlrtm1Her homozygotes (6-fold)
• when fed a high fat diet, mice exhibit a lesser increase in VLDL and LDL (3-fold) compared to Ldlrtm1Her homozygotes (6-fold)
• when fed a high fat diet, mice exhibit a reduced increase of 2.5-fold in liver cholesterol content compared to 11-fold in similarly treated Ldlrtm1Her homozygotes
• female mice develop skin lesions when fed a high fat diet
• total skin cholesterol content is increased 12- to 13-fold and 5.5-fold for free cholesterol compared to in Ldlrtm1Her homozygotes

liver/biliary system
• when fed a high fat diet, mice exhibit smaller diameter lipid droplets than in Ldlrtm1Her homozygotes
• when fed a high fat diet, mice exhibit an accumulation of inflammatory cells such as neutrophils and leukocytes around the hepatic vein unlike in Ldlrtm1Her homozygotes
• when fed a high fat diet, mice exhibit a reduced increase of 2.5-fold in liver cholesterol content compared to 11-fold in similarly treated Ldlrtm1Her homozygotes

endocrine/exocrine glands
• when fed a high fat diet, mice exhibit an decrease in cholesterol content, specifically esterified cholesterol, in the adrenal gland compared to in similarly treated Ldlrtm1Her homozygotes
• when fed a high fat diet, mice exhibit a severe depletion of cytoplasmic lipid droplets unlike in Ldlrtm1Her homozygotes

integument
• when fed a high fat diet, mice develop a thickened dermal layer with macrophage infiltrate and cholesterol deposits
• dermal thickening associated with a high fat diet is more severe in female mice than male mice
• when fed a high fat diet, female mice develop skin lesions beginning at 9 weeks with scratching and lesion areas that progress until animals cease eating and drinking
• skin lesions observed in mice fed a high fat diet are different than the non-fatal skin thickening observed in similarly treated Ldlrtm1Her homozygotes
• when fed a high fat diet, female mice exhibit severe ulcerations on thickened skin of the abdomen, neck and front limbs
• when fed a high fat diet, female mice develop pruritus (itching) and must be euthanized before the end of the 16 week study period


Mouse Genome Informatics
cx26
    Gpr132tm1Witt/Gpr132tm1Witt
Ldlrtm1Her/Ldlrtm1Her

B6.129-Ldlrtm1Her Gpr132tm1Witt
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cardiovascular system
• area in lesions occupied by macrophage is significantly increased
• reduced collagen content
• decreased apoptosis of macrophage in lesions

immune system
• decreased apoptosis of macrophage in atherosclerotic lesions

cellular
• decreased apoptosis of macrophage in atherosclerotic lesions

hematopoietic system
• decreased apoptosis of macrophage in atherosclerotic lesions


Mouse Genome Informatics
cx27
    Ldlrtm1Her/Ldlrtm1Her
Tcra-Jtm1Tgi/Tcra-Jtm1Tgi

B6.129-Ldlrtm1Her Tcra-Jtm1Tgi
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cardiovascular system
• lesions in the ascending aorta are reduced 20% in males and 28% in females relative to homozygous Ldlrtm1Her
• considerable reduction of lipid containing areas in the lesions
• less IFN-gamma in the lesions

immune system
• less IFN-gamma in atherosclerotic lesions


Mouse Genome Informatics
cx28
    Ldlrtm1Her/Ldlrtm1Her
Tlr2tm1Kir/Tlr2tm1Kir

B6.129-Tlr2tm1Kir Ldlrtm1Her
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
• reduced total plasma cholesterol on a high fat diet relative to Ldlrtm1Her/tm1Her controls

growth/size
• increased body weight on a high fat diet relative to Ldlrtm1Her/tm1Her controls (J:102502)

cardiovascular system
• aortic lesion area and aortic valve lesion volume are significantly reduced relative to Ldlrtm1Her/tm1Her controls (J:102502)
• less lipid accumulation in the lesser aortic curvature on a high fat diet than in Ldlrtm1Her/tm1Her controls (J:131783)

immune system
• leukocyte accumulation under the aortic endothelium is less than in Ldlrtm1Her/tm1Her controls
• significantly reduced response to LPS challenge

cellular
• leukocyte accumulation under the aortic endothelium is less than in Ldlrtm1Her/tm1Her controls

hematopoietic system
• leukocyte accumulation under the aortic endothelium is less than in Ldlrtm1Her/tm1Her controls


Mouse Genome Informatics
cx29
    Cd1d1tm1Luc/Cd1d1tm1Luc
Ldlrtm1Her/Ldlrtm1Her

B6.129S-Cd1d1tm1Luc Ldlrtm1Her
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cardiovascular system
• male mice after 4 weeks on the Western diet have lesions of small fatty streaks on the aorta were 40.4% smaller than Ldlrtm1Her
• Oil red O stained serial sections of 4-week-old mice fed a western diet, revealed had 31.7% less lipid staining than Ldlrtm1Her

homeostasis/metabolism
• slightly lower levels of very low density lipoprotein


Mouse Genome Informatics
cx30
    Ctsstm1Hap/Ctsstm1Hap
Ldlrtm1Her/Ldlrtm1Her

B6.129S-Ctsstm1Hap Ldlrtm1Her
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cardiovascular system
• after 12 and 26 weeks on an atherogenic diet with decreased macrophage, leukocyte, and CD4+ T cells within lesions

immune system
• leukocytes exhibit impaired leukocyte transmigration compared with wild-type cells

homeostasis/metabolism
• when fed standard chow

muscle

cellular
• leukocytes exhibit impaired leukocyte transmigration compared with wild-type cells

hematopoietic system
• leukocytes exhibit impaired leukocyte transmigration compared with wild-type cells


Mouse Genome Informatics
cx31
    Cxcl16/Zmynd15tm1Ifc/Cxcl16/Zmynd15tm1Ifc
Ldlrtm1Her/Ldlrtm1Her

B6.129S-Ldlrtm1Her Cxcl16/Zmynd15tm1Ifc
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cardiovascular system
• after 6 weeks, atherosclerosis lesions are 46% larger than in Ldlrtm1Her homozygotes
• after 10 weeks, atherosclerosis lesions are 27% and 56% (when assessed with serial sections of the aortic root stained with oil red O) larger than in Ldlrtm1Her homozygotes
• atherosclerotic lesions contain 80% more apoptotic cells than in Ldlrtm1Her homozygotes

cellular
• atherosclerotic lesions contain 80% more apoptotic cells than in Ldlrtm1Her homozygotes


Mouse Genome Informatics
cx32
    Ldlrtm1Her/Ldlrtm1Her
Cxcl16/Zmynd15tm1Ifc/Cxcl16/Zmynd15tm1Ifc

B6.129S-Ldlrtm1Her Cxcl16/Zmynd15tm1Ifc
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cardiovascular system
• after 6 weeks, atherosclerosis lesions are 46% larger than in Ldlrtm1Her homozygotes
• after 10 weeks, atherosclerosis lesions are 27% and 56% (when assessed with serial sections of the aortic root stained with oil red O) larger than in Ldlrtm1Her homozygotes
• atherosclerotic lesions contain 80% more apoptotic cells than in Ldlrtm1Her homozygotes

cellular
• atherosclerotic lesions contain 80% more apoptotic cells than in Ldlrtm1Her homozygotes


Mouse Genome Informatics
cx33
    Ldlrtm1Her/Ldlrtm1Her
Pfn1tm1Wit/Pfn1+

B6.129S-Ldlrtm1Her Pfn1tm1Wit
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• produced at a lower than expected ratio
• mice surviving to adulthood are healthy and normal regardless of diet fed

cardiovascular system
• lesions are reduced by 60% in males and 75% in females after 2 months on a high cholesterol diet as compared to Ldlr deficient mice
• less area in lesions is occupied by macrophage
• macrophage recruitment to lesion sites is reduced early in lesion formation

immune system
• macrophage recruitment to atherosclerotic lesion sites is reduced early in lesion formation
• ess area in lesions is occupied by macrophage

cellular
• macrophage recruitment to atherosclerotic lesion sites is reduced early in lesion formation
• ess area in lesions is occupied by macrophage

hematopoietic system
• macrophage recruitment to atherosclerotic lesion sites is reduced early in lesion formation
• ess area in lesions is occupied by macrophage


Mouse Genome Informatics
cx34
    Ldlrtm1Her/Ldlrtm1Her
Serpine1tm1Mlg/Serpine1tm1Mlg

B6.129S-Serpine1tm1Mlg Ldlrtm1Her
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cardiovascular system
• when fed a high fat Western diet for 6-30 weeks, mice develop atherosclerotic aortic lesions of the intimal and medial areas; incidence and severity are similar for Serpine1-deficient or transgenic Ldlr-deficient genotypes

homeostasis/metabolism
• mice develop severe cholesterolemia when receiving a high fat diet from 6 to 30 weeks (elevated levels are detected at 6, 15, and 30 weeks)


Mouse Genome Informatics
cx35
    Ldlrtm1Her/Ldlrtm1Her
Vwftm1Wgr/Vwftm1Wgr

B6.129S-Vwftm1Wgr Ldlrtm1Her
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cardiovascular system
• at 22 weeks, mice fed an atherogenic diet exhibit decreased atherosclerotic lesions size with fewer macrophages and reduced calcification compared with similarly treated Ldlrtm1Her homozygotes
• lesions in mice fed an atherogenic diet are uniformly distributed unlike in similarly treated Ldlrtm1Her homozygotes that exhibit formation hot spots
• however, mice exhibit normal atherosclerotic lesions at 37 weeks

immune system
• leukocyte rolling on a chow diet is decreased compared to in wild-type mice
• however, rolling on an atherogenic diet is normal

cellular
• leukocyte rolling on a chow diet is decreased compared to in wild-type mice
• however, rolling on an atherogenic diet is normal

hematopoietic system
• leukocyte rolling on a chow diet is decreased compared to in wild-type mice
• however, rolling on an atherogenic diet is normal


Mouse Genome Informatics
cx36
    Ifngtm1Ts/Ifngtm1Ts
Ldlrtm1Her/Ldlrtm1Her

B6.129S7-Ldlrtm1Her Ifngtm1Ts
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cardiovascular system
• after 8 or 20 weeks on a cholesterol diet aortic lesion size is reduced compared to mice homozygous for Ldlrtm1Her alone

hematopoietic system
• increase in the proportion of T cells in the blood relative to controls homozygous for Ldlrtm1Her alone

immune system
• increase in the proportion of T cells in the blood relative to controls homozygous for Ldlrtm1Her alone


Mouse Genome Informatics
cx37
    Ldlrtm1Her/Ldlrtm1Her
Mobq5CAST/Ei/Mobq5CAST/Ei

B6.CAST-Mobq5CAST/Ei
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
• decreased plasma cholesterol
• decreased unesterified cholesterol


Mouse Genome Informatics
cx38
    Ldlrtm1Her/Ldlrtm1Her
Mobq6CAST/Ei/Mobq6CAST/Ei

B6.CAST-Mobq6CAST/Ei
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
• decreased obesity on a Western diet
• decreased plasma cholesterol
• decreased unesterified cholesterol
• improved glucose tolerance on a Western diet

cardiovascular system
• reduced aortic root lesion size (2-3 fold smaller)

behavior/neurological
• increased food efficiency

growth/size
• decreased obesity on a Western diet


Mouse Genome Informatics
cx39
    Crptm1Hjf/Crptm1Hjf
Ldlrtm1Her/Ldlrtm1Her

B6.Cg-Crptm1Hjf Ldlrtm1Her
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
• in male mice at 20 weeks
• in male mice at 20 weeks
• in male mice at 20 weeks

cardiovascular system
• female mice exhibit an increase in macrophage content in lesions compared with Ldlrtm1Her homozygotes
• however, lesion size and susceptibility do not differ from Ldlrtm1Her homozygotes


Mouse Genome Informatics
cx40
    Ins2Akita/Ins2Akita
Ldlrtm1Her/Ldlrtm1Her

B6.Cg-Ins2Akita Ldlrtm1Her
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• compared with Ldlrtm1Her homozygotes

homeostasis/metabolism
• severe compared with Ldlrtm1Her homozygotes
• in fasting mice compared with Ldlrtm1Her homozygotes
• in fasting mice compared with Ldlrtm1Her homozygotes
• in female mice compared with Ldlrtm1Her homozygotes
• 2-fold in male mice and 24% in female mice compared with Ldlrtm1Her homozygotes
• 7-fold in male mice and 1.8-fold in female mice compared with Ldlrtm1Her homozygotes
• in fasting mice compared with Ldlrtm1Her homozygotes
• compared with Ldlrtm1Her homozygotes

growth/size
• in male, but not female, mice at 20 weeks of age compared with Ldlrtm1Her homozygotes

cardiovascular system
• accelerated in mice fed a high-fat diet compared with similarly treated Ldlrtm1Her homozygotes


Mouse Genome Informatics
cx41
    Ldlrtm1Her/Ldlrtm1Her
Scd1ab-2J/Scd1ab-2J

B6.Cg-Ldlrtm1Her Scd1ab-2J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype

Adiposity in Ldlrtm1Her/Ldlrtm1Her and Scd1ab-2J/Scd1ab-2J Ldlrtm1Her/Ldlrtm1Her mice

adipose tissue
• when fed a western style diet for 12 weeks, mice exhibit a 50% reduction in total fat mass compared to in Ldlrtm1Her homozygotes
• when fed a western style diet for 12 weeks, male mice have smaller periepididymal fat pads than Ldlrtm1Her homozygotes
• when fed a western style diet for 12 weeks, female mice have smaller periuterine fat pads than Ldlrtm1Her homozygotes

homeostasis/metabolism
N
• when fed a western style diet for 12 weeks, mice are protected from impaired glucose tolerance, hyperglycemia, and increased plasma insulin levels observed in Ldlrtm1Her homozygotes (J:130278)
• when fed a western style diet for 12 weeks, mice exhibit a decrease in visceral and subcutaneous lipid compared to in Ldlrtm1Her homozygotes
• when fed a western style diet for 12 weeks, male mice exhibit a lower circulating cholesterol level than in Ldlrtm1Her homozygotes
• compared to in Ldlrtm1Her homozygotes when fed a western style diet for 12 weeks
• when fed a western style diet for 12 weeks, female mice exhibit a lower circulating triglyceride level than in Ldlrtm1Her homozygotes
• compared to in Ldlrtm1Her homozygotes when fed a western style diet for 12 weeks
• when fed a western style diet for 12 weeks, mice exhibit a 5-fold lower hepatic triglyceride level than in Ldlrtm1Her homozygotes

behavior/neurological
• when fed a western style diet for 12 weeks, mice consuming more food than Ldlrtm1Her homozygotes

growth/size
• when fed a western style diet for 12 weeks, mice exhibit a 50% reduction in total fat mass compared to in Ldlrtm1Her homozygotes
• when fed a western style diet for 12 weeks, mice gain less weight than Ldlrtm1Her homozygotes despite consuming more food

liver/biliary system
N
• when fed a western style diet for 12 weeks, mice are protected from the hepatic steatosis observed in Ldlrtm1Her homozygotes (J:130278)
• when fed a western style diet for 12 weeks, mice exhibit a 5-fold lower hepatic triglyceride level than in Ldlrtm1Her homozygotes


Mouse Genome Informatics
cx42
    Ldlrtm1Her/Ldlrtm1Her
Scd1ab-J/Scd1ab-J

B6.Cg-Ldlrtm1Her Scd1ab-J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
adipose tissue
• when fed a western style diet for 12 weeks, mice exhibit a 50% reduction in total fat mass compared to in Ldlrtm1Her homozygotes
• when fed a western style diet for 12 weeks, male mice have smaller periepididymal fat pads than Ldlrtm1Her homozygotes
• when fed a western style diet for 12 weeks, female mice have smaller periuterine fat pads than Ldlrtm1Her homozygotes

homeostasis/metabolism
N
• when fed a western style diet for 12 weeks, mice are protected from impaired glucose tolerance, hyperglycemia and increased plasma insulin levels observed in Ldlrtm1Her homozygotes (J:130278)
• when fed a western style diet for 12 weeks, mice exhibit a decrease in visceral and subcutaneous lipid compared to in Ldlrtm1Her homozygotes
• when fed a western style diet for 12 weeks, male mice exhibit a lower circulating cholesterol level than in Ldlrtm1Her homozygotes
• compared to in Ldlrtm1Her homozygotes when fed a western style diet for 12 weeks
• when fed a western style diet for 12 weeks, mice exhibit a 5-fold lower hepatic triglyceride level than in Ldlrtm1Her homozygotes
• when fed a western style diet for 12 weeks, female mice exhibit a lower circulating triglyceride level than in Ldlrtm1Her homozygotes
• when fed a western style diet for 12 weeks, female mice exhibit a lower circulating triglyceride level than in Ldlrtm1Her homozygotes
• compared to in Ldlrtm1Her homozygotes when fed a western style diet for 12 weeks
• when fed a western style diet for 12 weeks, mice exhibit a 5-fold lower hepatic triglyceride level than in Ldlrtm1Her homozygotes

behavior/neurological
• when fed a western style diet for 12 weeks, mice consuming more food than Ldlrtm1Her homozygotes

growth/size
• when fed a western style diet for 12 weeks, mice exhibit a 50% reduction in total fat mass compared to in Ldlrtm1Her homozygotes
• when fed a western style diet for 12 weeks, mice gain less weight than Ldlrtm1Her homozygotes despite consuming more food

liver/biliary system
N
• when fed a western style diet for 12 weeks, mice are protected from the hepatic steatosis observed in Ldlrtm1Her homozygotes (J:130278)
• when fed a western style diet for 12 weeks, mice exhibit a 5-fold lower hepatic triglyceride level than in Ldlrtm1Her homozygotes


Mouse Genome Informatics
cx43
    Ldlrtm1Her/Ldlrtm1Her
Tg(CMV-Serpine1)1Dgi/0

B6.Cg-Ldlrtm1Her Tg(CMV-Serpine1)1Dgi
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cardiovascular system
• when fed a high fat Western diet for 6-30 weeks, mice develop atherosclerotic aortic lesions of the intimal and medial areas; incidence and severity are similar for Serpine1-deficient or transgenic Ldlr-deficient genotypes

homeostasis/metabolism
• mice develop severe cholesterolemia receiving a high fat diet from 6 to 30 weeks (elevated levels are detected at 6, 15, and 30 weeks)


Mouse Genome Informatics
cx44
    Ldlrtm1Her/Ldlrtm1Her
Lepob/Lepob

B6.Cg-Lepob Ldlrtm1Her
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cardiovascular system
• extensive atherosclerotic lesions throughout the aorta by 6 months of age

homeostasis/metabolism
• plasma contains severely elevated and broadened lipoprotein peak, ranging from VLDL/LDL-sized particles to LDL-sized particles
• age dependent increase in cholesterol levels between 1 and 4 months of age, with maximal values at 3-4 months of age (1715 mg/dl vs. 81 mg/dl in wild-type), followed by a gradual decrease by 8 months
• fasting, diet restriction, and low-level leptin treatment only slightly lowers plasma cholesterol levels
• elevated at 3 and 8 months of age
• age dependent increase in triglyceride levels between 1 and 4 months of age, with maximal values at 3-4 months of age, followed by a gradual decrease by 8 months
• fasting, diet restriction, and low-level leptin treatment significantly lowers plasma triglyceride levels
• livers exhibit slightly, but significantly, higher levels of cholesterol
• livers exhibit about 10x higher levels of triglyceride

liver/biliary system
• livers exhibit slightly, but significantly, higher levels of cholesterol
• livers exhibit about 10x higher levels of triglyceride

Mouse Models of Human Disease
OMIM IDRef(s)
Hypercholesterolemia, Familial 143890 J:72027


Mouse Genome Informatics
cx45
    Ldlrtm1Her/Ldlr+
Lepob/Lepob

B6.Cg-Lepob Ldlrtm1Her
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
• age dependent increase in cholesterol levels between 1 and 4 months of age, with maximal values at 3-4 months of age (282 mg/dl vs 81 md/dl in wild-type) that are maintained thereafter
• slightly elevated at 3 and 8 months of age
• livers exhibit slightly, but significantly, higher levels of cholesterol
• livers exhibit about 10x higher levels of triglyceride, however no increase in plasma triglyceride levels

liver/biliary system
• livers exhibit slightly, but significantly, higher levels of cholesterol
• livers exhibit about 10x higher levels of triglyceride, however no increase in plasma triglyceride levels


Mouse Genome Informatics
cx46
    Apoetm1Unc/Apoetm1Unc
Ldlrtm1Her/Ldlrtm1Her

involves: 129P2/OlaHsd * 129S7/SvEvBrd
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
• plasma cholesterol on a high fat diet reaches 4120 mg/dl
• triglyceride levels are unaffected by diet


Mouse Genome Informatics
cx47
    Ldlrtm1Her/Ldlrtm1Her
Mapkapk2tm1Mgl/Mapkapk2tm1Mgl

involves: 129P2/OlaHsd * 129S7/SvEvBrd * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cardiovascular system
• reduced development of atherosclerosis after 8-16 weeks on an atherogenic diet

hematopoietic system
• reduced in number among peritoneal macrophage in mice fed an atherogenic diet for 10 weeks
• decreased macrophage content in longitudinal sections of the aortic arch

homeostasis/metabolism
• increased plasma cholesterol relative to mice deficient only in Ldlr
• increased non-HDL cholesterol relative to mice deficient only in Ldlr

immune system
• reduced in number among peritoneal macrophage in mice fed an atherogenic diet for 10 weeks
• decreased macrophage content in longitudinal sections of the aortic arch

cellular
• reduced in number among peritoneal macrophage in mice fed an atherogenic diet for 10 weeks


Mouse Genome Informatics
cx48
    Ldlrtm1Her/Ldlrtm1Her
Lipctm1Unc/Lipctm1Unc

involves: 129P2/OlaHsd * 129S7/SvEvBrd * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
• levels in response to ACTH are significantly reduced
• levels markedly increased
• primarily in HDL and LDL fractions


Mouse Genome Informatics
cx49
    Lcattm1Hgc/Lcattm1Hgc
Ldlrtm1Her/Ldlrtm1Her

involves: 129P2/OlaHsd * 129S7/SvEvBrd * C57BL/6 * DBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
N
• unlike Lcat single mutants, the free cholesterol/esterfied cholesterol ratio is not significantly different from controls (J:75567)
• fasting glucose levels are 31% lower than the single mutant controls
• fasting insulin levels are 42% lower than the single mutant controls
• increase in APOB-100
• about a 2 fold decrease in all plasma lipid constituents compared to mice homozygous null for Lcat and Apoe (J:75567)
• unlike in Ldlr single mutants, the long chain PUFA, 20:4, 20:5 n-3 and 22:6 n-3 esters are absent (J:75567)
• 8 fold increase in triglyceride production rate compared to single mutant controls (J:89015)
• increase in plasma triglyceride levels compared to Ldlr single mutants (J:75567)
• 1.7 fold increase in fasting triglyceride levels compared to single mutant littermate controls (J:89015)
• most of the excess triglycerides are concentrated in the VLDL fractions; however, both the LDL and IDL fractions are enriched for triglycerides (J:89015)
• compared to Ldlr single mutants the APOB lipoprotein cholesterol ester composition has increases in the 16:0, 18:0, and 18:1 esters and decreases in the 18:2 esters (J:75567)
• there is a 7 fold increase in the ratio of saturated + monounsaturated/polyunsaturated cholesterol ester fatty acid species compared to controls (J:75567)
• total plasma free cholesterol : cholesterol ester ratio is significantly increased compared to controls (J:89015)
• no detectable HDL (J:75567)
• severely reduced (J:89015)
• decrease in the LDL/IDL fractions compared to controls
• increase in free cholesterol level compared to Ldlr single mutants
• increase in the cholesterol level in the VLDL fraction (J:89015)
• decrease in post heparin lipase activity


Mouse Genome Informatics
cx50
    Apoetm1Unc/Apoetm1Unc
Ldlrtm1Her/Ldlrtm1Her

involves: 129P2/OlaHsd * 129S7/SvEvBrd * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cardiovascular system
• two out of 8 hypoxic hearts show thrombosis as well as atherosclerotic plaques
• elevated STU segment as a result of induced hypoxia
• noticeable at 16% oxygen concentration
• ECG is corrected by 10 minutes after restoration of normal oxygen
• hypoxia response unaffected by treatment with a thrombin inhibitor
• mice treated with a thrombin inhibitor display lower Troponin-T levels and fewer fibrinogen + cells than untreated mice 48 hours after hypoxia
• in mice treated with a thrombin inhibitor 48 hours after hypoxia
• infarctions are irregular in shape and subendocardial or intramural

homeostasis/metabolism
• mice treated with a thrombin inhibitor display lower Troponin-T levels and fewer fibrinogen + cells than untreated mice 48 hours after hypoxia
• in mice treated with a thrombin inhibitor 48 hours after hypoxia
• infarctions are irregular in shape and subendocardial or intramural

nervous system
• elevated cholesterol in the exofacial leaflet of the synaptic plasma membrane but not so high as for Ldlr deficient mice with normal Apoe alleles
• cholesterol levels in the cytofacial leaflet are reduced
• cholesterol/phospholipid ratio in the synaptic plasma membrane is elevated but not so much as for Ldlr deficient mice with normal Apoe alleles


Mouse Genome Informatics
cx51
    Ldlrtm1Her/Ldlrtm1Her
Nr0b2tm1.1Mjev/Nr0b2tm1.1Mjev

involves: 129S/SvEvBrd * 129S4/SvJae * 129S7/SvEvBrd * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
N
• mice fed a Western diet fail to exhibit an increase in triglyceride and VLDL cholesterol levels unlike wild-type mice (J:149005)
• when fed a high fat diet
• mice fed a Western diet exhibit a reduced elevation in LDL cholesterol levels compared with similarly treated Ldlrtm1Her homozygotes


Mouse Genome Informatics
cx52
    Ddr1tm1Wfv/Ddr1tm1Wfv
Ldlrtm1Her/Ldlrtm1Her

involves: 129S1/Sv * 129S7/SvEvBrd * 129X1/SvJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cardiovascular system
• pronounced reduction in atherosclerotic plaques after 12 and 24 weeks on a high fat diet
• 50% reduction in plaque area in the descending aorta at 12 weeks
• 60% reduction in plaque area in the descending aorta at 24 weeks
• total collagen and elastin in plaques is elevated at 12 weeks
• total collagen and elastin in plaques is at control levels at 24 weeks
• increased synthesis and decreased degradation of collagen and elastin at 12 weeks

hematopoietic system
• few macrophage in plaques at 12 weeks
• macrophage numbers in plaques similar to controls at 24 weeks

immune system
• few macrophage in plaques at 12 weeks
• macrophage numbers in plaques similar to controls at 24 weeks


Mouse Genome Informatics
cx53
    Ldlrtm1Her/Ldlrtm1Her
Pcsk9tm1.2Prat/Pcsk9tm1.2Prat

involves: 129S1/Sv * 129S7/SvEvBrd * 129X1/SvJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
• plasma levels are increased 14.8 fold relative to controls
• plasma HDL levels are unaffected


Mouse Genome Informatics
cx54
    Cxcl1tm1Wabo/Cxcl1tm1Wabo
Ldlrtm1Her/Ldlrtm1Her

involves: 129S1/Sv * 129S7/SvEvBrd * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cardiovascular system
• surface lesions in aortas are significantly smaller than those in Ldlr homozygous, Cxcl wild-type littermates (14.2% vs 17.1%)
• lesion area in the aoritic valve is smaller than in littermates (186,423 micron2 vs 238636 micron2
• there is less macrophage accumualation in lesions of double knockouts than in control single mutants
• double knockouts are less susceptible than Ldlr single knockouts


Mouse Genome Informatics
cx55
    Esr1tm1.1Mma/Esr1tm1.1Mma
Ldlrtm1Her/Ldlrtm1Her

involves: 129S2/SvPas * 129S7/SvEvBrd
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
• estrogen fails to prevent fatty streak deposits in the aorta of these mice as it does in Ldlr null homozygote controls

cardiovascular system
• lacking functional Ldlr receptors makes this mice prone to developing atherosclerosis


Mouse Genome Informatics
cx56
    Alox15tm1Fun/Alox15tm1Fun
Ldlrtm1Her/Ldlrtm1Her

involves: 129S2/SvPas * 129S7/SvEvBrd * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cardiovascular system
• reduced atherosclerotic lesions when fed a high fat diet for 3 or 9 weeks


Mouse Genome Informatics
cx57
    Itgb3tm1Hyn/Itgb3tm1Hyn
Ldlrtm1Her/Ldlrtm1Her

involves: 129S2/SvPas * 129S7/SvEvBrd * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• at 16 weeks of age after 10 weeks on a western style diet only 52% of mice survive compared to 100% survival for diet matched Ldlr single mutants
• no increase in mortality is seen in mice kept on a standard chow diet
• at 16 weeks of age after 10 weeks on a western style diet only 52% of mice survive compared to 100% survival for diet matched Ldlr single mutants

homeostasis/metabolism
• the level after 10 weeks on a western diet is higher than in diet matched Ldlr single mutants
• cholesterol levels after 6 and 10 weeks on a western diet are lower than in diet matched Ldlr single mutants

cardiovascular system
• on a western style diet, lesions are 2.0 fold greater at the arch and 4.1 fold greater at the thoracic aorta compared to diet matched Ldlr single mutants


Mouse Genome Informatics
cx58
    Icam1tm1Jcgr/Icam1tm1Jcgr
Ldlrtm1Her/Ldlrtm1Her

involves: 129S4/SvJae * 129S7/SvEvBrd
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
hematopoietic system
• neutrophil counts are increased when mice have been on an 8-week cholesterol-enriched diet compared to homozygous Ldlr mice, however develop aortic lesions to the same extent as homozygous Ldlr mice

immune system
• neutrophil counts are increased when mice have been on an 8-week cholesterol-enriched diet compared to homozygous Ldlr mice, however develop aortic lesions to the same extent as homozygous Ldlr mice


Mouse Genome Informatics
cx59
    Apobec1tm1Chan/Apobec1tm1Chan
Ldlrtm1Her/Ldlrtm1Her

involves: 129S4/SvJae * 129S7/SvEvBrd
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
• circulating VLDL/LDL cholesterol levels are increased compared to in Ldlrtm1Her homozygotes, Apobec1tm1Chan homozygotes, and wild-type mice
• when fed a chow diet or Western-type diet for 2 and 4 weeks, mice exhibit increased serum cholesterol levels compared with Ldlrtm1Her homozygotes, Apobec1tm1Chan homozygotes, and wild-type mice
• when fed a Western-type diet for 14 weeks, mice exhibit higher serum cholesterol levels compared with Ldlrtm1Her homozygotes
• when fed a Western-type diet for 2 weeks, serum triglyceride levels are less than in Ldlrtm1Her homozygotes
• when fed a chow diet or a high fat diet for 2 and 4 weeks, mice exhibit a decrease in serum triglyceride levels compared with Apobec1tm1Chan homozygotes and wild-type mice


Mouse Genome Informatics
cx60
    Ldlrtm1Her/Ldlrtm1Her
Vcam1tm2Cyb/Vcam1tm2Cyb

involves: 129S4/SvJae * 129S7/SvEvBrd * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cardiovascular system
• develop fewer early foam cell lesions in the aorta than homozygous Ldlr mice after an 8 week cholesterol-enriched diet, however cholesterol levels, lipoprotein profiles and leukocyte numbers are similar to wild-type


Mouse Genome Informatics
cx61
    Icam1tm1Jcgr/Icam1tm1Jcgr
Ldlrtm1Her/Ldlrtm1Her
Vcam1tm2Cyb/Vcam1tm2Cyb

involves: 129S4/SvJae * 129S7/SvEvBrd * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cardiovascular system
• after an 8-week cholesterol-enriched diet, whole aorta and arch lesion area is reduced by 31% and 45%, respectively, compared to double homozygous Icam1 and Ldlr mice, and by 48% and 38%, respectively, compared to single homozygous Ldlr mutant mice

homeostasis/metabolism
• after an 8-week cholesterol-enriched diet, develop a less severe hypercholesterolemia than single homozygous Ldlr mutant mice

immune system
• total leukocyte counts are increased when mice have been on an 8-week cholesterol-enriched diet compared to homozygous Ldlr mutant mice
• neutrophil counts are increased when mice have been on an 8-week cholesterol-enriched diet compared to homozygous Ldlr mutant mice
• lymphocyte counts are increased when mice have been on an 8-week cholesterol-enriched diet compared to homozygous Ldlr mutant mice
• monocyte counts are increased when mice have been on an 8-week cholesterol-enriched diet compared to homozygous Ldlr mutant mice

hematopoietic system
• total leukocyte counts are increased when mice have been on an 8-week cholesterol-enriched diet compared to homozygous Ldlr mutant mice
• neutrophil counts are increased when mice have been on an 8-week cholesterol-enriched diet compared to homozygous Ldlr mutant mice
• lymphocyte counts are increased when mice have been on an 8-week cholesterol-enriched diet compared to homozygous Ldlr mutant mice
• monocyte counts are increased when mice have been on an 8-week cholesterol-enriched diet compared to homozygous Ldlr mutant mice


Mouse Genome Informatics
cx62
    Apobec1tm1Ddsn/Apobec1tm1Ddsn
Ldlrtm1Her/Ldlrtm1Her

involves: 129S4/SvJae * 129S7/SvEvBrd * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
• total cholesterol levels are higher in males than females
• on a high fat diet total cholesterol reaches 1600 mg/dl by 8 weeks
• elevated in both sexes but higher in males than females

cardiovascular system
• extensive lesions along the length of the aorta at 8 months
• lesions are somewhat more extensive in males but otherwise the sexes are similar
• on a high fat diet lesions cover 9% of the aorta surface by 8 weeks

Mouse Models of Human Disease
OMIM IDRef(s)
Hypercholesterolemia, Familial 143890 J:49125


Mouse Genome Informatics
cx63
    Ldlrtm1Her/Ldlrtm1Her
Pparatm1Gonz/Pparatm1Gonz

involves: 129S4/SvJae * 129S7/SvEvBrd * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
N
• fasting glucose levels and insulin levels are not increased after dexamethasone treatment (J:84844)

growth/size
• after dexamethasone treatment

adipose tissue
• after dexamethasone treatment


Mouse Genome Informatics
cx64
    Ccl2tm1Rol/Ccl2tm1Rol
Ldlrtm1Her/Ldlrtm1Her

involves: 129S4/SvJae * 129S7/SvEvBrd * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cardiovascular system
• when fed a high fat diet, mice exhibit decreased incidence of atherosclerosis, lipid deposition, and macrophage infiltration of aortic arches compared with similarly treated Ldlrtm1Her homozygotes

homeostasis/metabolism
• compared to in Ldlrtm1Her homozygotes
• compared to in Ldlrtm1Her homozygotes


Mouse Genome Informatics
cx65
    Ldlrtm1Her/Ldlrtm1Her
Soat1tm1Far/Soat1tm1Far

involves: 129S4/SvJae * 129S7/SvEvBrd * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype

Soat1tm1Far/Soat1tm1Far Ldlrtm1Her/Ldlrtm1Her mice fed an atherogenic diet for 2 months display severe xanthomatosis

homeostasis/metabolism
• serum total cholesterol levels in mutants fed the atherogenic diet for 2 months are lower than in single Ldlr homozygotes
• skin of mutants fed an atherogenic diet shows edematous lesions
• double mutants fed an atherogenic diet for 2 months develop severe dermal xanthomatosis; skin shows diffuse deposition of cholesterol crystals in both the reticular and papillary dermis

cardiovascular system
• mutants fed a Western diet develop atherosclerotic lesions
• aortic lesion composition differs from that in Apoe homozygotes, with lower neutral lipid content and fewer cholesterol crystals

immune system
• severe, pleomorphic inflammatory reaction accompanies the cholesterol deposition in atherogenic diet fed mutants, however the features are different from those in double Soat1 and Apoe mutants
• inflammatory cells are predominantly macrophages, lymphocytes, and plasma cells, with fewer neutrophils than in double Soat1 and Apoe mutants

nervous system
• mutants fed an atherogenic diet exhibit crystalline cholesterol deposits in the brains, particularly near the choroid plexus and in the cerebellum
• mutants fed an atherogenic diet exhibit crystalline cholesterol deposits in the cerebellum

integument
• skin of mutants fed an atherogenic diet shows edematous lesions
• severe, pleomorphic inflammatory reaction accompanies the cholesterol deposition in atherogenic diet fed mutants, however the features are different from those in double Soat1 and Apoe mutants
• inflammatory cells are predominantly macrophages, lymphocytes, and plasma cells, with fewer neutrophils than in double Soat1 and Apoe mutants
• diffuse deposition of cholesterol crystals in the reticular and papillary dermis of mutants fed an atherogenic diet
• skin lesions are seen only when mutants are fed a Western diet and not when fed a chow diet
• mutants fed an atherogenic diet, but not a chow diet, develop diffuse, massive thickening of the skin compared to single Ldlr mutants
• however, do not develop skin excoriations, hair loss or pruritic skin


Mouse Genome Informatics
cx66
    Ldlrtm1Her/Ldlrtm1Her
Scarb1tm1Dhu/Scarb1tm1Dhu

involves: 129S4/SvJae * BALB/c * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cardiovascular system
• lesion size is significantly increased in males compared to LDL-receptor controls


Mouse Genome Informatics
cx67
    Angptl3tm1Lex/Angptl3tm1Lex
Ldlrtm1Her/Ldlrtm1Her

involves: 129S5/SvEvBrd * 129S7/SvEvBrd * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
• serum cholesterol levels are 60% lower than in Ldlr null homozygote controls
• serum triglyceride levels are 86% lower than in Ldlr null homozygote controls


Mouse Genome Informatics
cx68
    Ldlrtm1Her/Ldlrtm1Her
Tbx21tm1Glm/Tbx21tm1Glm

involves: 129S6/SvEvTac * 129S7/SvEvBrd * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype

Phenotype of aortic arch atherosclerotic lesions in Tbx21tm1Glm/Tbx21tm1Glm Ldlrtm1Her/Ldlrtm1Her and Ldlrtm1Her/Ldlrtm1Her mice

cardiovascular system
• atherosclerosis in both aortic arch and descending aorta is significantly reduced compared with Ldlrtm1Her homozygotes and lesions have less smooth muscle content
• males have an 81% reduction in the aortic arch intimal area of lesions and 49% reduction in descending aorta compared with control males, however no differences seen in females
• after 8 weeks of proatherogenic diet, intimal smooth muscle cell content is lower in aortic arch than in controls, indicating a delay in evolution of lesions

homeostasis/metabolism
• hypercholesterolemic; cholesterol levels are no different from those in Ldlrtm1Her homozygotes

immune system
• significant reduction of total IgG2a compared to Ldlrtm1Her homozygotes; IgG2a titers to both MDA-LDL and CuOx-LDL are reduced or absent
• IgG1 titers to both antigens (MDA-LDL and CuOx-LDL) are reduced despite similar total levels of IgG1
• exhibit a more than 2.5-fold increase in the titer of atheroprotective E06 natural IgM antibodies compared to Ldlrtm1Her homozygotes
• unlike CD4+ T cells in Ldlrtm1Her homozygotes on a high cholesterol diet, T cells do not produce significant amounts of IFN-gamma upon polyclonal stimulation with anti-CD3 and upon stimulation with plaque antigen hsp60
• on a high cholesterol diet, higher levels of IL-4, IL-5, and IL-10 are produced upon anti-CD3 stimulation and higher levels of IL-5 and IL-10 upon hsp60 stimulation of T cells compared to T cells from Ldlrtm1Her homozygotes

hematopoietic system
• significant reduction of total IgG2a compared to Ldlrtm1Her homozygotes; IgG2a titers to both MDA-LDL and CuOx-LDL are reduced or absent
• IgG1 titers to both antigens (MDA-LDL and CuOx-LDL) are reduced despite similar total levels of IgG1
• exhibit a more than 2.5-fold increase in the titer of atheroprotective E06 natural IgM antibodies compared to Ldlrtm1Her homozygotes


Mouse Genome Informatics
cx69
    Esr1tm1Arnal/Esr1tm1Arnal
Ldlrtm1Her/Ldlrtm1Her

involves: 129S7/SvEvBrd
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
• estrogen fails to prevent fatty streak deposits in the aorta of these mice as it does in Ldlr null homozygote controls

cardiovascular system
• lacking functional Ldlr receptors makes these mice prone to developing atherosclerosis


Mouse Genome Informatics
cx70
    Ldlrtm1Her/Ldlrtm1Her
Olr1tm1Meht/Olr1tm1Meht

involves: 129S7/SvEvBrd * 129X1/SvJ * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
• when fed a high-cholesterol diet, NMR proton spectra of lipids indicates a level of photon intensity for HDL of 0.77 compared to 0.83 in wild-type mice
• when fed a high cholesterol diet, NMR proton spectra of lipids indicates a level of photon intensity for LDL of 0.88 compared to 0.84 in wild-type mice
• when fed a high cholesterol diet, NMR proton spectra of lipids indicates a level of photon intensity for VLDL of 0.92 compared to 0.88 in wild-type mice
• IL-10 levels are increased compared to in Ldlrtm1Her homozygotes

cardiovascular system
• mice exhibit less intimal thickening and sudanophilic areas than in Ldlrtm1Her homozygotes
• mice do not exhibit endothelial disruption as in Ldlrtm1Her homozygotes

immune system
• IL-10 levels are increased compared to in Ldlrtm1Her homozygotes


Mouse Genome Informatics
cx71
    Ldlrtm1Her/Ldlrtm1Her
Npc1m1N/Npc1m1N

involves: 129S7/SvEvBrd * BALB/c
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• mice die between 80 and 100 days of age from neurodegenerative disease

nervous system
• mice have decreased levels of total cholesterol in the brain
• reduced in size by 50% at 11 weeks of age
• glial cells reduced by 44%
• axonal swelling by 11 weeks of age
• small reduction in Purkinje cell numbers in the cerebellar hemispheres at 3 weeks of age
• reduction in numbers increases with age
• glial cells in the corpus callosum reduced by 44%

homeostasis/metabolism
• mice have decreased levels of total cholesterol in the brain
• mice have increased cholesterol levels in the liver, spleen, intestine and lung to a greater extant than that observed in Npc1 mutants on a wild-type background
• plasma LDL levels are increased 15-fold in these mice (J:130969)


Mouse Genome Informatics
cx72
    Ldlrtm1Her/Ldlrtm1Her
Npc1m1N/Npc1m1N

involves: 129S7/SvEvBrd * BALB/c * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• some early death among males on a high fat 1% cholesterol diet

liver/biliary system
• in mice on a high fat, 1% cholesterol diet
• increased liver weight to 14% of body weight in mice that die early
• liver reaches 22% of body weight in mice that live longer


Mouse Genome Informatics
cx73
    Asgr2tm1Her/Asgr2tm1Her
Ldlrtm1Her/Ldlrtm1Her

involves: 129S7/SvEvBrd * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
• double homozygotes display a plasma lipoprotein profile that is similar to that of single Ldlrtm1Her mutant mice
• notably, double homozygotes do not accumulate any chylomicron remnants in their plasma


Mouse Genome Informatics
cx74
    Soat1tm1Ishi/Soat1tm1Ishi
Ldlrtm1Her/Ldlrtm1Her

involves: 129S7/SvEvBrd * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype

Cutaneous xanthomatosis and alopecia in Soat1tm1Ishi/Soat1tm1Ishi Apoetm1Unc/Apoetm1Unc and Soat1tm1Ishi/Soat1tm1Ishi Ldlrtm1Her/Ldlrtm1Her mice

vision/eye

homeostasis/metabolism
• adrenocortical lipid depletion
• increased serum cholesterol levels
• hypercholesterolemia
• cutaneous xanthomatosis

endocrine/exocrine glands

integument


Mouse Genome Informatics
cx75
    Ldlrtm1Her/Ldlrtm1Her
Tg(APOC1)1Lmh/?

involves: 129S7/SvEvBrd * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
• elevated levels of serum cholesterol, mainly confined to the VLDL-sized fraction
• elevated levels of serum triglyceride, mainly confined to the VLDL-sized fraction


Mouse Genome Informatics
cx76
    Apoetm1Lmh/Apoetm1Lmh
Ldlrtm1Her/Ldlrtm1Her

involves: 129S7/SvEvBrd * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
N
• mice show normal FVIII (Factor 8) levels in plasma (J:117317)


Mouse Genome Informatics
cx77
    Apobtm2Sgy/Apobtm2Sgy
Ldlrtm1Her/Ldlrtm1Her

involves: 129S7/SvEvBrd * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
vision/eye
• age related accumulation of esterified cholesterol in the basement of the retinal pigment epithelial layer
• losses in rod and cone sensitivity only after 14 months of age

pigmentation
• age related accumulation of esterified cholesterol in the basement of the retinal pigment epithelial layer


Mouse Genome Informatics
cx78
    Ldlrtm1Her/Ldlrtm1Her
Tg(APOM)NCchr/0

involves: 129S7/SvEvBrd * C57BL/6 * C57BL/6J * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cardiovascular system
• when fed a high cholesterol diet, mice exhibit a smaller plaque size compared to Ldlrtm1Her homozygotes (neutral-lipid staining area is reduced by 39%, collagen staining area is reduced 30%)
• when fed a high cholesterol diet, en face lesion area in the aortic arch is 3.1+/-0.5% compared to 6.6+/-1.8% in Ldlrtm1Her homozygotes

homeostasis/metabolism
• 0.85+/-0.07 mmol/l compared to 1.11+/-0.10 mmol/l in Ldlrtm1Her homozygotes at 4 weeks on a high cholesterol diet
• when fed a high cholesterol diet, free cholesterol is decreased (0.31+/-0.02 nmol/mm2 compared to 0.37+/-0.02 nmol/mm2 in Ldlrtm1Her homozygotes)


Mouse Genome Informatics
cx79
    Ldlrtm1Her/Ldlrtm1Her
Tg(Il1rn)1Dih/Tg(Il1rn)1Dih

involves: 129S7/SvEvBrd * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cardiovascular system
• when fed high-cholesterol, high-fat diet containing cholate for 4 weeks, 40% decrease in atherosclerosis lesion size when compared to homozygous single Ldlr mutant mice

homeostasis/metabolism
• 40% increase in total plasma cholesterol (non-HDL) when fed cholesterol-fat enriched Western diet for 10 weeks; slight increase in total plasma cholesterol level when fed high-cholesterol, high-fat diet containing cholate for 4 weeks
• 40% increase in total plasma triglyceride level when fed cholesterol-fat enriched Western diet for 10 weeks

Mouse Models of Human Disease
OMIM IDRef(s)
Hypercholesterolemia, Familial 143890 J:76336


Mouse Genome Informatics
cx80
    Ldlrtm1Her/Ldlrtm1Her
Tg(H2-K-AKR1B1)1Tj/0

involves: 129S7/SvEvBrd * C57BL/6 * DBA/2
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
• streptozotocin (STZ) treatment leads to 3-fold higher level of blood glucose in mice fed a high fat diet
• these high glucose levels persist for at least 12 weeks after STZ treatment
• streptozotocin (STZ) induced diabetes in mice fed a high fat diet leads to blood cholesterol levels that are twice those of non-diabetic mice 6 weeks post-induction
• blood cholesterol levels increase to three times greater than in non-diabetic mice 8 weeks after STZ treatment

cardiovascular system
• non-diabetic mice fed a high fat diet have a total lesion area of 10.7% in their aortas compared to 8.0% in Ldlr tm1Her homozyogotes that do not carry the transgene
• diabetic mice fed a high fat diet for 6 weeks have a total aortic lesion area of 37.5% compared to 23.4% lesion area in diabetic Ldlr tm1Her homozyogotes that do not carry the transgene
• these differences in aortic lesion area between transgenic and non-transgenic Ldlr tm1Her homozyogotes increase the longer the mice are on a high fat diet
• the greatest differences are observed in the aortic arch of diabetic mice where there is a 65% increase in the lesion area 6 weeks after disease induction compared to Ldlr tm1Her homozyogotes that do not carry the transgene

immune system
• peritoneal macrophages have a higher uptake of acetylated LDL compared macrophages from Ldlr tm1Her homozyogotes that do not carry the transgene
• mean uptake of acetylated-LDL is 5.27 micrograms/mg cellular protein vs 1.18 micrograms/mg cellular protein in controls

hematopoietic system
• peritoneal macrophages have a higher uptake of acetylated LDL compared macrophages from Ldlr tm1Her homozyogotes that do not carry the transgene
• mean uptake of acetylated-LDL is 5.27 micrograms/mg cellular protein vs 1.18 micrograms/mg cellular protein in controls


Mouse Genome Informatics
cx81
    Ldlrtm1Her/Ldlr+
Tg(H2-K-AKR1B1)1Tj/0

involves: 129S7/SvEvBrd * C57BL/6 * DBA/2
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
• streptozotocin (STZ) treatment leads to 3-fold higher level of blood glucose in mice fed a high fat diet
• these high glucose levels persist for at least 12 weeks after STZ treatment

cardiovascular system
• in mice made diabetic by STZ treatment and fed a cholesterol/cholic acid containing diet for 12 weeks, total aortic lesion area is doubled compared to Ldlr tm1Her heterozygotes that do not carry the transgene
• the presence of the transgene causes no difference in lesion size in non-diabetic mice


Mouse Genome Informatics
cx82
    Apobtm2Sgy/Apobtm2Sgy
Ldlrtm1Her/Ldlrtm1Her
Tg(Ins-Igf2)1Fbos/?

involves: 129S7/SvEvBrd * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
• elevated relative to mice lacking the transgene at 6 months regardless of diet
• difference from controls lacking the transgene persists on a high fat diet but not on a normal diet at 15 months
• plasma insulin levels are 2X control levels at 6 months in fed mice and fasted mice on a high fat diet
• fasted mice on a normal diet do not show elevated insulin
• reduced insulin sensitivity over the course of an insulin tolerance test
• sustained elevation of blood glucose during a glucose tolerance test regardless of diet
• blood insulin is unchanged over the course of a glucose tolerance test

cardiovascular system
• lesion thickness increases more on a high fat diet than does lesion area
• increased calcification of lesions after 15 months on a high fat diet, particularly for females


Mouse Genome Informatics
cx83
    Ldlrtm1Her/Ldlrtm1Her
Tg(APPSWE)2576Kha/0

involves: 129S7/SvEvBrd * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
• make more entries into the open arms of an elevated plus maze on day 2 of testing
• fail to show intersession habituation over 3 days of testing in an open field, unlike transgenic mice wild-type for Ldlr
• learning impairment in a Morris water maze at 10 months of age
• impairment not affected by Ldlr genotype
• at 13 months of age mice trained at 10 months of age are slower to reacquire the location of the hidden platform in a morris water maze compared to transgenic mice wild-type for Ldlr
• in a probe trial mice fail to occupy the target quadrant longer than chance indicating memory retention deficits
• relative to non-transgenic controls

homeostasis/metabolism
• hypercholesterolemia with the increase in the non-HDL fraction
• increase is mainly in the LDL fraction
• age dependent cerebral amyloidosis
• plaques first appear in the hippocampus and cortex at around 11 months
• progressive accumulation in the brain after 11 months
• cerebral amyloid beta deposition is increased compared to transgenic mice wild-type for Ldlr

nervous system
• cerebral amyloid beta deposition is increased compared to transgenic mice wild-type for Ldlr

Mouse Models of Human Disease
OMIM IDRef(s)
Alzheimer Disease; AD 104300 J:114480


Mouse Genome Informatics
cx84
    Ldlrtm1Her/Ldlrtm1Her
Lrpap1tm1Her/Lrpap1tm1Her

involves: 129S7/SvEvBrd * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
• chylomicron reminent and LDL levels increased in blood
• 2 fold increase in total plasma cholesterol
• moderately increased plasma triglyceride levels


Mouse Genome Informatics
cx85
    Ldlrtm1Her/Ldlrtm1Her
Nceh1tm1Ishi/Nceh1tm1Ishi

involves: 129S7/SvEvBrd * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cardiovascular system
• depending on the statistical method, the atherosclerotic lesion surface area is increased 1.6- to 3.1-fold compared to in Ldlrtm1Her homozygotes


Mouse Genome Informatics
cx86
    Ldlrtm1Her/Ldlrtm1Her
Lipetm1Ishi/Lipetm1Ishi

involves: 129S7/SvEvBrd * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cardiovascular system
• depending on the statistical method, the atherosclerotic lesion surface area is increased 1.2 -to 1.7-fold compared to in Ldlrtm1Her homozygotes


Mouse Genome Informatics
cx87
    Ldlrtm1Her/Ldlrtm1Her
Lipetm1Ishi/Lipetm1Ishi
Nceh1tm1Ishi/Nceh1tm1Ishi

involves: 129S7/SvEvBrd * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cardiovascular system
• depending on the statistical method, the atherosclerotic lesion surface area is increased 2.0- to 4.3-fold compared to in Ldlrtm1Her homozygotes


Mouse Genome Informatics
cx88
    Ldlrtm1Her/Ldlrtm1Her
Tg(APOC3)3707Bres/?

involves: 129S7/SvEvBrd * C57BL/6J * CBA/J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
• DL-LDL levels increased about 2 fold over the 32mg/dl level found in mice carrying only the transgene
• 3-4 fold increase in IDL-LDL on a Western diet over the 86mg/dl level found in mice carrying only the transgene but also on a Western diet
• increased 10 fold over the level of 50mg/dl or less found in mice carrying only the transgene
• more pronounced increase when fed a Western diet

cardiovascular system
• lesions at the base of the aorta are 2-3 times the size of lesions in mice lacking the transgene but homozygous for Ldlr deficiency

Mouse Models of Human Disease
OMIM IDRef(s)
Hyperlipidemia, Familial Combined; FCHL 144250 J:37861


Mouse Genome Informatics
cx89
    Ldlrtm1Her/Ldlrtm1Her
Tg(APOC3)3707Bres/?
Tg(Mt1-CETP)#Tall/?

involves: 129S7/SvEvBrd * C57BL/6J * CBA/J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
• lowered by 79% on a normal diet
• lowered by 36% on a Western diet
• cholesterol shifted from HDL to IDL-LDL and VLDL
• cholesterol shifted from HDL to IDL-LDL and VLDL
• cholesterol shifted from HDL to IDL-LDL and VLDL
• triglycerides shifted from VLDL to IDL-LDL and HDL


Mouse Genome Informatics
cx90
    Cx3cl1tm1Sgs/Cx3cl1tm1Sgs
Ldlrtm1Her/Ldlrtm1Her

involves: B6.129S4-Cx3cl1tm1Sgs * B6.129S7-Ldlrtm1Her/J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cardiovascular system
• aortic-root lesion area is reduced in females by 35% but not reduced in males
• brachiocephalic artery lesion area is reduced in female double homozygotes by about 50% at 200 um from its branching site into the carotid and subclavian arteries

homeostasis/metabolism
• the decrease in total serum cholesterol is mainly due to a decrease in LDL cholesterol

immune system
• macrophage accumulation is reduced by 57% in the brachiocephalic artery at 200 um from its branching site into the carotid and subclavian arteries

cellular
• macrophage accumulation is reduced by 57% in the brachiocephalic artery at 200 um from its branching site into the carotid and subclavian arteries

hematopoietic system
• macrophage accumulation is reduced by 57% in the brachiocephalic artery at 200 um from its branching site into the carotid and subclavian arteries


Mouse Genome Informatics
cx91
    Cx3cl1tm1Sgs/Cx3cl1tm1Sgs
Ldlrtm1Her/Ldlr+

involves: B6.129S4-Cx3cl1tm1Sgs * B6.129S7-Ldlrtm1Her/J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cardiovascular system
• aortic-root lesion area is reduced in females by 28% but not reduced in males

homeostasis/metabolism
• total serum cholesterol is reduced in male but not female mutants


Mouse Genome Informatics
cx92
    Ath37CAST/Ei/Ath37CAST/Ei
Ldlrtm1Her/Ldlrtm1Her

involves: CAST/Ei * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cardiovascular system
• 43% decreased atherosclerotic lesion size on a high fat diet


Mouse Genome Informatics
cx93
    Ath38CAST/Ei/Ath38CAST/Ei
Ldlrtm1Her/Ldlrtm1Her

involves: CAST/Ei * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cardiovascular system
• 41% decreased atherosclerotic lesion size on a high fat diet