Analysis Tools|
Allele Symbol Allele Name Allele ID |
Cbstm1Unc targeted mutation 1, University of North Carolina MGI:1857139 |
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| Summary |
13 genotypes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice exhibit serum homocysteine, total homocysteine, and methionine unlike in wild-type mice
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• serum total homocysteine levels are increased compared to in wild-type mice
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• mice exhibit decreased serum taurine levels compared to in wild-type mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• weigh an average of 20% less compared to wild-type controls from 3-8 months of age
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• plasma levels are 50-fold higher compared to wild-type controls
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• especially in the hypertrophic zone at 1 month of age but not at 3 months of age
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• increased width of the long bone cartilaginous growth plates
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• at 1 month of age
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• apparent by P15
• curvature is located in the thoracic vertebrae
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• severity progresses with age
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• shorter and thinner lumbar vertebrae
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• delayed differentiation at 1 month of age in long bones
• however by 3 months of age differences are no longer apparent
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• disorganized
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• at 1 month of age but mostly caught up by 3 months of age
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• digits are the same length as controls despite smaller body size with relatively elongated metatarsal and metacarpal bones
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• at P15
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• bent at the distal tip by P15
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| hyperhomocysteinemia | DOID:9279 |
OMIM:603174 |
J:112538 | |
|
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice fed a low cysteine diet fail to exhibit paralysis unlike similarly treated Cthtm1Iish homozygotes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• plasma levels of N-homocysteine are 8.1-fold higher than in wild-type mice
• total plasma homocysteine levels are higher than in wild-type mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
Abnormal hepatocyte morphology in Cbstm1Unc/Cbs+ and Cbstm1Unc/Cbstm1Unc mice
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• on a standard laboratory diet, homozygotes show a high incidence of lethality between 3 and 4 weeks after birth, with the majority dying within 5 weeks of age; only ~20% of the expected number is obtained at 5-12 weeks of age
(J:23321)
• dietary supplementation with choline at weaning extends postnatal survival to adulthood
(J:105571)
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• homozygotes are present at roughly the expected Mendelian frequency until P14; however, less than 60% of the expected number of homozygotes are obtained at 3 weeks of age
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• homozygotes dying at early postnatal stages have faces that are typical of very young animals
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• homozygotes display a pointed snout
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• at P21, most homozygotes appear runted relative to wild-type mice
(J:23321)
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• at P14, homozygotes display body weights that are only 80% of those found in wild-type or heterozygous mice
(J:23321)
• at 3 weeks, homozygotes weigh significantly less than wild-type mice
(J:105571)
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• homozygotes show a progressive failure in weight gain after P7; differences in body weight become pronounced between P14 and P21
(J:23321)
• a few homozygotes surviving >2 months display normal stature at weaning and maintain a relatively normal body size until just before death
(J:23321)
• on a choline-enriched diet, adult homozygotes exhibit growth retardation, weighing an average of 20% less than wild-type or heterozygous mice
(J:105571)
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• occasionally, older female homozygotes (one 3-mo-old and one 6-mo-old) show hepatomegaly with subtle autolyic changes
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• at 8- and 12 weeks, mutant livers exhibit a significantly increased proapoptotic Bax/Bcl-2 ratio (up to 16 vs. 1 arbitrary unit), suggesting induction of a mitochondrial apoptotic pathway
• however, no caspase-3 activation, DNA fragmentation, or TUNEL-positive cells are detected at 12 weeks or later, suggesting that protective signals may counteract apoptotic signals, leading to chronic inflammation
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• occasionally, older female homozygotes (one 3-mo-old and one 6-mo-old) show hepatomegaly with subtle autolyic changes
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• on a choline-enriched diet, 8-week-old and ageing homozygotes display mild hepatic inflammation, with foci of perilobular mononuclear inflammatory infiltrates around the vessels
• however, no hepatocyte necrosis is detected up to 32 weeks age
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• at P14-P21, mutant hepatocytes appear enlarged and pleiomorphic, with a 2-fold increase in mean diameter and enlarged nuclei; multi- and binucleated hepatocytes are present
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• on a standard laboratory diet, homozygotes develop hepatic steatosis at ~P15, with lipid droplets containing triacylglycerols and cholesteryl esters
• on a choline-enriched diet, homozygotes exhibit a mild, localized hepatic steatosis (grade 1) at 12 and 18 weeks, which progresses to extensive grade 2 steatosis by 32 weeks of age
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• at P21, some mutant hepatocytes contain microvesicular cytoplasmic lipid droplets
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• on a standard laboratory diet, homozygotes develop hepatic fibrosis at ~P15
• on a choline-enriched diet, 8-week-old homozygotes display a mild hepatic perivascular fibrosis which progresses to pericellular fibrosis at week 12 and portal fibrosis by week 32, along with a ~50-fold increase in liver collagen content
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• at P21, mutant livers show a light tan color instead of a normal reddish-brown color
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• at 3 months, homozygotes show a 20-fold increase in mean hepatic homocysteine levels relative to wild-type mice
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• at P21, F2 homozygotes show plasma homocysteine levels that are ~40 times higher than those of age-matched wild-type mice
(J:23321)
• at 3 months, homozygotes fed a choline-enriched diet, show a 50-fold increase in total plasma homocysteine levels relative to similarly fed wild-type mice
(J:105571)
• pregnant females show a significant increase in total plasma homocysteine levels from day 4 to day 16 of gestation
(J:190486)
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• on day 6 after mating with vasectomized males, plasma progesterone levels are significantly higher in pseudo-pregnant female homozygotes relative to their wild-type counterparts
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• at P21, one of 4 homozygotes display hemosiderin deposits in spleen
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• on day 8 of gestation, a significant increase in protein levels of alpha-fetoprotein is detected in decidual cells
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• at 8- and 12 weeks, mutant livers display significantly higher IL-6 mRNA levels relative to wild-type livers
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• at 8- and 12 weeks, mutant livers display significantly higher TNF mRNA levels relative to wild-type livers; CD14 mRNA levels are also increased, confirming Kuppfer cell activation and elevated TNF production
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• on day 8 of gestation, a significant decrease in uterine NK cells expressing granzyme b is observed in the decidua basalis
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• no uterine NK cells are histologically detected on day 12 of gestation; instead, implantation sites are filled with connective tissue
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• at P21, mutant (but not wild-type) hepatocytes display extramedullary hematopoiesis
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• at P21, mutant knee joints appear immature relative to wild-type joints
• homozygotes dying at early postnatal stages display tails and extremities of smaller diameters relative to their length
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• homozygotes dying at early postnatal stages display tails and extremities of smaller diameters relative to their length
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• on day 12 of gestation, no consolidation of decidua is observed, unlike in wild-type pregnant females; instead, tissue degeneration is accompanied by necrosis
(J:190486)
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• on day 18 of gestation, the thickness of decidual layer is reduced in placentas from pregnant female homozygotes, indicating reduced trophoblast invasion in these females
(J:114850)
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• on day 8 of gestation, a significant decrease in uterine NK cells expressing granzyme b is observed in the decidua basalis
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• no uterine NK cells are histologically detected on day 12 of gestation; instead, implantation sites are filled with connective tissue
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• in response to the ovulatory surge of hCG, female homozygotes develop less follicles than wild-type females, indicating a reduced response to pregnant mare serum gonadotropin
• in addition, superovulated female homozygotes display an increased Oil red O staining of lipids in the ovarian corpora lutea relative to wild-type females
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• female homozygotes show a striking decrease in gravid uterine weight relative to wild-type females; this is accompanied by significant reductions in placental and fetal weights
• notably, the endometrium, muscular layer and perimetrium appear histologically normal
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• infertile female homozygotes show a shorter and irregular estrus cycle
• both estrus and diestrus periods are decreased while the metestrus is prolonged
• differences in estrus cycle have no effect over the number of oocytes ovulated during normal estruses, although the yield is much lower when female homozygotes are superovulated
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• when 90-day-old female homozygotes are mated with homologous male partners, pregnancy loss occurs between day 8 and day 12 of gestation (during placenta formation), with significant decreases in the mass of dissected uteri and embryos from day 8 to day 16
(J:190486)
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• despite a similar number of implantation sites, the percentage of surviving fetuses in homozygous pregnant females is severely reduced relative to wild-type pregnant females
(J:114850)
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• as both mutant ovaries and ovulated oocytes appear morphologically normal, authors suggest that uterine dysfunction is a consequence of either hyperhomocysteinemia or other factor(s) in the uterine environment
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• transcriptomic analyses of implantation and interimplantation sites showed impaired decidualization and altered gene expression networks in the uterus on day 8 of gestation
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• female homozygotes surviving >2months fail to reproduce
(J:23321)
• female homozygotes show normal sexual behavior but are infertile due to uterine failure
(J:114850)
• fertility is restored when homozygous mutant ovaries are transplanted to normal ovarectomized recipients
(J:114850)
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• matings between female x male homozygotes result in a drastic reduction of litter size, since five homozygous females had only two born pups, which died soon after birth, versus 39 obtained with heterozygous females
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• at P21, mutant eyes appear immature relative to wild-type or heterozygous eyes; however, no ocular pathology is observed
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• at P21, most homozygotes exhibit smaller eyes
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• homozygotes dying at early postnatal stages show delayed eyelid opening
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• at P21, mutant lungs appear immature relative to wild-type or heterozygous lungs
|
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• at P21, mutant kidneys appear immature relative to wild-type or heterozygous kidneys
|
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• at P21, mutant hearts appear immature relative to wild-type or heterozygous hearts
• no thrombi are detected in vascular segments or other tissues
|
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• homozygotes dying at early postnatal stages have faces that are typical of very young animals
|
|
• homozygotes display a pointed snout
|
|
• on day 8 of gestation, a significant decrease in uterine NK cells expressing granzyme b is observed in the decidua basalis
|
|
• no uterine NK cells are histologically detected on day 12 of gestation; instead, implantation sites are filled with connective tissue
|
|
• at 3 months, homozygotes exhibit hyperplastic sebaceous glands
|
|
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• in response to the ovulatory surge of hCG, female homozygotes develop less follicles than wild-type females, indicating a reduced response to pregnant mare serum gonadotropin
• in addition, superovulated female homozygotes display an increased Oil red O staining of lipids in the ovarian corpora lutea relative to wild-type females
|
|
• at 8- and 12 weeks, mutant livers exhibit a significantly increased proapoptotic Bax/Bcl-2 ratio (up to 16 vs. 1 arbitrary unit), suggesting induction of a mitochondrial apoptotic pathway
• however, no caspase-3 activation, DNA fragmentation, or TUNEL-positive cells are detected at 12 weeks or later, suggesting that protective signals may counteract apoptotic signals, leading to chronic inflammation
|
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• at 3 months, homozygotes exhibit accelerated maturation of keratinocytes
|
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• at 3 months, mutant livers exhibit enhanced protein oxidation and lipid peroxidation, as shown by a ~30% increase in oxidatively modified proteins (carbonyls) and a similar increase in MDA and 4-HNE aldehydes, respectively
• hepatic oxidative stress may cause mitochondrial damage in association with activation of hepatic Kuppfer (stellate) cells, leading to liver injury
|
|
• on day 8 of gestation, a significant decrease in uterine NK cells expressing granzyme b is observed in the decidua basalis
|
|
• no uterine NK cells are histologically detected on day 12 of gestation; instead, implantation sites are filled with connective tissue
|
|
• at 8- and 12 weeks, mutant livers display significantly higher IL-6 mRNA levels relative to wild-type livers
|
|
• at 8- and 12 weeks, mutant livers display significantly higher TNF mRNA levels relative to wild-type livers; CD14 mRNA levels are also increased, confirming Kuppfer cell activation and elevated TNF production
|
|
• on a choline-enriched diet, 8-week-old and ageing homozygotes display mild hepatic inflammation, with foci of perilobular mononuclear inflammatory infiltrates around the vessels
• however, no hepatocyte necrosis is detected up to 32 weeks age
|
|
• on day 12 of gestation, no consolidation of decidua is observed, unlike in wild-type pregnant females; instead, tissue degeneration is accompanied by necrosis
(J:190486)
|
|
|
|
• on day 18 of gestation, the thickness of decidual layer is reduced in placentas from pregnant female homozygotes, indicating reduced trophoblast invasion in these females
(J:114850)
|
|
• on day 8 of gestation, a significant decrease in uterine NK cells expressing granzyme b is observed in the decidua basalis
|
|
• no uterine NK cells are histologically detected on day 12 of gestation; instead, implantation sites are filled with connective tissue
|
|
• on day 18 of gestation, the junctional zone is reduced in placentae of female homozygotes
|
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• on day 18 of gestation, the labyrinthine zone is enlarged in placentae of female homozygotes
|
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• on day 18 of gestation, female homozygotes display a decrease of placental mass that correlates with the presence of weakened layers
(J:114850)
• placental weight is significantly decreased on day 12 of gestation
(J:190486)
|
|
• transcriptomic analyses of implantation and interimplantation sites showed impaired decidualization and altered gene expression networks in the uterus on day 8 of gestation
|
|
• at 3 months, homozygotes exhibit accelerated maturation of keratinocytes
|
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• at 3 months, homozygotes exhibit hyperplastic sebaceous glands
|
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• homozygotes lack a normal healthy fur; in contrast, vibrissae, eyelids and nails appear normal
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• at 3 months, homozygotes exhibit a sparse fur on their head and a more dense fur on their backs
• homozygotes display a variable reduction in the (mid-shaft) diameter of back, abdominal, and head hairs
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• at 3 months, homozygotes display a thinner hypodermis
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• at 3 months, mutant hair roots extend deeper into the subcutaneous fatty tissues while the basal portion of the follicles remains in the hypodermis
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• homozygotes exhibit an increased number of hair follicles on their backs
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• at 3 months, homozygotes show a thin dermis; however, epidermal-dermal junctions appear normal
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• at 3 months, homozygotes epidermal hyperkeratosis
• however, melanocyte morphology appears normal, and no changes in hair or skin color are observed
|
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• at 3 months, the mutant epidermis displays enlarged spinous cells, in the absence of increased proliferation
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| homocystinuria | DOID:9263 |
OMIM:236200 OMIM:236250 |
J:105571 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• on a low-folate diet, heterozygotes exhibit siginifcantly elevated plasma total homocysteine levels relative to wild-type mice
(J:64885)
• however, on a control diet, heterozygotes display normal plasma total homocysteine levels relative to wild-type mice
(J:64885)
• serum total homocysteine levels are slightly increased compared to in wild-type mice
(J:166184)
|
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• capillary tufts and dilations are seen in peripheral areas of the retina
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• at 24 weeks of age, mice have large vessels that manifest numerous small constrictions along their length, giving them a saccular, beaded appearance instead of smooth edges as in wild-type mice
• increase in blood vessel tortuosity in the retina
• increase in venule, but not arteriole, width, in the retina and a decrease in the ratio of arteriole/venule width
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• a well-defined branching pattern from the central retinal artery is not seen in mutant mice and a large capillary-free zone is seen in the central part of the retina
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• by 1 year of age, many microaneurysms are seen in the capillary bed and there is evidence of new blood vessels
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• at 52 weeks of age, mice show evidence of new vessels in the retina and marker analysis indicates neovascularization in multiple layers of the retina, including the ganglion cell and inner nuclear layers
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• in the retina, pericytes are partially detached and extend processes away from the endothelial cells
• retinal blood vessels show pericytes with degenerated cytoplasmic remnants and occasionally ghosts of former pericytes
• retinas show pericyte disruption in nearly all blood vessels (>90%) compared to <5% in wild-type mice
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• increase in venule, but not arteriole, width, in the retina and a decrease in the ratio of arteriole/venule width
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• evidence of vascular occlusion in the retina, ischemic nodules, and hemorrhagic spots
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• on a low-folate diet (~50% reduction in plasma folate levels), heterozygotes display a significant endothelial vasomotor dysfunction associated with moderate hyperhomocysteinemia
• endothelial vasomotor dysfunction is noted only in mice with a combined defect in homocysteine remethylation (produced by dietary folate deficiency) and homocysteine transsulfuration (produced by heterozygous deficiency)
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• vascular leakage is seen within the capillary bed of the retina at 24 weeks of age
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• on a control diet, heterozygotes show normal relaxation of aortic rings in response to the endothelium-dependent vasodilator acetylcholine relative to wild-type mice
• however, on a low-folate diet, heterozygotes exhibit impaired maximal relaxation of aortic rings in response to acetylcholine relative to wild-type mice (58 9% vs 84 4%, respectively)
• no significant differences in relaxation to nitroprusside or contraction to the thromboxane A2 analog U-46619 are observed between wild-type and heterozygous mice fed either control or low-folate diets
• no significant differences in aortic thrombomodulin activity are observed between wild-type and heterozygous mice fed either control or low-folate diets
|
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• on a control diet, heterozygotes show normal relaxation of aortic rings in response to the endothelium-dependent vasodilator acetylcholine relative to wild-type mice
• however, on a low-folate diet, heterozygotes exhibit impaired maximal relaxation of aortic rings in response to acetylcholine relative to wild-type mice (58 9% vs 84 4%, respectively)
• no significant differences in relaxation to nitroprusside or contraction to the thromboxane A2 analog U-46619 are observed between wild-type and heterozygous mice fed either control or low-folate diets
• no significant differences in aortic thrombomodulin activity are observed between wild-type and heterozygous mice fed either control or low-folate diets
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• Muller cell activation in the retina
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• astrocytes in the retina have diffuse branching patterns and a ragged appearance
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• retinas show an increase in astrocytes which have diffuse branching patterns and a ragged appearance
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• fluorescein angiography of retinas shows leakage of fluorescein at 24 weeks of age that progresses with age indicating vascular leakage
• marker analysis indicates disruption of the inner blood-retinal barrier
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• fluorescein angiography of retinas shows leakage of fluorescein at 24 weeks of age that progresses with age indicating vascular leakage
• marker analysis indicates disruption of the inner blood-retinal barrier
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• disruption of retinal architecture and the inner retina has an uneven appearance in 52 week old mice
• retinas show hypoxic areas, particularly in the regions where there is abnormal vasculature
|
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• capillary tufts and dilations are seen in peripheral areas of the retina
|
|
• at 24 weeks of age, mice have large vessels that manifest numerous small constrictions along their length, giving them a saccular, beaded appearance instead of smooth edges as in wild-type mice
• increase in blood vessel tortuosity in the retina
• increase in venule, but not arteriole, width, in the retina and a decrease in the ratio of arteriole/venule width
|
|
• a well-defined branching pattern from the central retinal artery is not seen in mutant mice and a large capillary-free zone is seen in the central part of the retina
|
|
• by 1 year of age, many microaneurysms are seen in the capillary bed and there is evidence of new blood vessels
|
|
• at 52 weeks of age, mice show evidence of new vessels in the retina and marker analysis indicates neovascularization in multiple layers of the retina, including the ganglion cell and inner nuclear layers
|
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• Muller cell activation in the retina
|
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• reactive gliosis in the retina
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• disruption of retinal architecture is seen in 52 week old mice, with unusual structures within the vitreous and debris in the vitreous cavity
|
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• ischemia in the central retina and new blood vessel formation in the periphery
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| homocystinuria | DOID:9263 |
OMIM:236200 OMIM:236250 |
J:213631 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• plasma levels are 2-fold higher compared to wild-type controls
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| hyperhomocysteinemia | DOID:9279 |
OMIM:603174 |
J:112538 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
Abnormal hepatocyte morphology in Cbstm1Unc/Cbs+ and Cbstm1Unc/Cbstm1Unc mice
|
• at P21, heterozygotes show a 2-fold increase in plasma homocysteine levels relative to wild-type mice
• homocysteine concentrations decrease with age in wild-type and heterozygous mice, reaching levels of 3 nmol/ml and 7 nmol/ml, respectively, by 22 weeks of age
|
|
• hepatocytes have anisonucleosis and fairly prominent nucleoli and appear to be slightly larger
|
| N |
• at 3 months, heterozygotes display normal skin and hair morphology
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• liver N-homocysteine levels in zinc-induced mice are 3.4-fold higher than in Cbstm1Unc Tg(Mt1-CBS)25Waku heterozygotes
• N-homocysteine levels are 3.3-fold lower than in Cbstm1Unc/Cbstm1Unc Tg(MT1-CBS*I278T)1Waku mice
|
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• plasma N-homocysteine levels in zinc-induced mice are 4.2-fold higher than Cbstm1Unc Tg(Mt1-CBS)25Waku heterozygotes
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• liver N-homocysteine levels in zinc-induced mice are 11.5-fold higher than in Cbstm1Unc Tg(Mt1-CBS* I278T)1Waku heterozygotes or Tg(Mt1-CBS* I278T)1Waku mice
• total liver homocysteine levels in zinc-induced mice are 51- to 75-fold higher than in Cbstm1Unc Tg(Mt1-CBS* I278T)1Waku heterozygotes or Tg(Mt1-CBS* I278T)1Waku mice
• N-homocysteine levels in zinc-induced mice are 3.3-fold greater than in Cbstm1Unc/Cbstm1Unc Tg(Mt1-CBS)25Waku mice
|
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• plasma N-homocysteine levels in zinc-induced mice are 6.3-fold to 10.6-fold higher than in Cbstm1Unc Tg(Mt1-CBS* I278T)1Waku heterozygotes or Tg(Mt1-CBS* I278T)1Waku mice
• total plasma homocysteine levels in zinc-induced mice are 54- to 143-fold higher than in Cbstm1Unc Tg(Mt1-CBS* I278T)1Waku heterozygotes or Tg(Mt1-CBS* I278T)1Waku mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• zinc-induced mice fed a high-fat diet exhibit increased atherosclerotic lesions compared to controls
• zinc-induced mice fed a high-fat diet exhibit enhanced Ly-6C monocyte/macrophage accumulation in atherosclerotic lesions
|
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• zinc-induced mice fed a high fat diet develop severe hyperhomocysteinemia associated with a 15.6% reduction in body weight
|
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• increase in monocyte population in blood, spleen, and bone marrow of 15 months old zinc-induced mice fed a regular diet
|
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• zinc-induced mice fed a regular diet with severe hyperhomocysteinemia exhibit elevated CD11b+Ly-6Chi and CD11b+Ly-6Cmid inflammatory monocyte subsets
|
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• plasma homocysteine levels are increased in zinc-induced mutants fed a regular or a high-fat diet
|
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• plasma methionine levels are increased in zinc-induced mutants fed a regular diet
• however, methionine levels are normal in zinc-induced mutants fed a high-fat diet
|
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• high-fat diet fed zinc-induced mice show increased plasma levels of the proinflammatory cytokine TNF-alpha and the chemotactic factor MCP-1
|
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• increase in monocyte population in blood, spleen, and bone marrow of 15 months old zinc-induced mice fed a regular diet
|
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• zinc-induced mice fed a regular diet with severe hyperhomocysteinemia exhibit elevated CD11b+Ly-6Chi and CD11b+Ly-6Cmid inflammatory monocyte subsets
|
|
• high-fat diet fed zinc-induced mice show increased plasma levels of the proinflammatory cytokine TNF-alpha and the chemotactic factor MCP-1
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| homocystinuria | DOID:9263 |
OMIM:236200 OMIM:236250 |
J:168131 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• increase in monocyte population in blood, spleen, and bone marrow of 6 month old zinc-induced mice with severe hyperhomocysteinemia which is further increased at 8 months of age
|
|
• zinc-induced mice with severe hyperhomocysteinemia exhibit elevated CD11b+Ly-6Chi and CD11b+Ly-6Cmid inflammatory monocyte subsets
|
|
• plasma N-homocysteine levels in zinc-induced mice are 6.4-fold to 12.8-fold higher than in Cbstm1Unc Tg(Mt1-CBS*S466L)EB86Waku heterozygotes or Tg(Mt1-CBS*S466L)EB86Waku mice
(J:150548)
• total plasma homocysteine levels in zinc-induced mice are higher than in Cbstm1Unc Tg(Mt1-CBS*S466L)EB86Waku heterozygotes or Tg(Mt1-CBS*S466L)EB86Waku mice
(J:150548)
• plasma homocysteine is greatly increased in 6 month old zinc-induced mice, with no further change at 8 months
(J:168131)
|
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• plasma methionine levels are slightly elevated and slightly increase with age in zinc-induced mice
|
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• increase in monocyte population in blood, spleen, and bone marrow of 6 month old zinc-induced mice with severe hyperhomocysteinemia which is further increased at 8 months of age
|
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• zinc-induced mice with severe hyperhomocysteinemia exhibit elevated CD11b+Ly-6Chi and CD11b+Ly-6Cmid inflammatory monocyte subsets
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mutants exhibit decreased survival after 80 days of age, however more than 50% are alive at 1 year of age
|
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• mutants exhibit decreased survival after 80 days of age, however more than 50% are alive at 1 year of age
|
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• plasma levels of S-adenosylmethionine (AdoMet), and S-adenosylhomocysteine (AdoHcy) are elevated 2.6-fold and 29-fold, respectively, compared to controls
• mutants treated with betaine exhibit lowering of AdoHcy, AdoMet, and cystathionine and increased levels of plasma methionine, dimethylglycine, methylglycine, and cysteine
|
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• plasma levels of methionine are elevated 2-fold and levels of cystathionine are elevated 4-fold compared to controls
• plasma cysteine levels are decreased about 5-fold compared to controls
• mutants treated with betaine exhibit increased levels of plasma methionine, dimethylglycine, methylglycine, and cysteine and lower cystathionine levels
|
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• plasma levels of total homocysteine are elevated 83-fold compared to controls
• mutants treated with betaine exhibit lowering of total homocysteine levels
|
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• analysis of tail bleeding times indicate that mutants clot about 3-fold faster than controls, indicating hypercoagulation
• treatment with betaine increases clotting time in mutants
|
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• tail bleeding times indicate that mice are in a hypercoagulative state
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• mutants exhibit signs of mild hepatopathy such as nuclear anisokoria and signs of hyperregeneration
• however no hepatic steatosis or fibrosis are seen and livers are normal in size and coloration
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| homocystinuria | DOID:9263 |
OMIM:236200 OMIM:236250 |
J:165612 | |
Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO) |
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last database update 11/19/2024 MGI 6.24 |
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