Analysis Tools
mortality/aging
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• about 40% die within the first hour of birth
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• 85% of mice die by P10 compared with 13% of wild-type mice
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growth/size/body
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• in response to transverse aortic constriction (TAC)-induced pressure overload, wild-type hearts exhibit a progressive cardiac hypertrophy with significant dilatory remodeling whereas mutant hearts show more modest and concentric cardiac hypertrophy at 3 weeks, with minimal further progression
• at 9 weeks after TAC, mutant hearts develop significantly less intestitial fibrosis, myocyte hypertrophy, and fetal gene re-expression (B-natriuretic peptide and alpha-skeletal actin) relative wild-type hearts
• however, homozygotes show no significant differences in baseline heart weight or myocyte size relative to wild-type mice
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• fetuses from E18 to term demonstrate slight growth retardation
(J:98913)
• Intrauterine Growth Retardation demonstrated by ultrasonographic imaging showing differences in embryo and gestational vesicle measurements in both longitudinal and transversal curves from Days 5.5 to 14.5.
(J:140819)
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cardiovascular system
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• after remnant kidney surgery, homozygotes exhibit a significantly greater endothelial cell loss than similarly-treated wild-type controls
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• after remnant kidney surgery, homozygotes exhibit a significantly greater decrease (50%) in endothelial cell density in the glomeruli and renal cortex relative to similarly-treated wild-type controls
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• abnormalities in pulmonary vascular development
• disorganization of the extracellular matrix structure in the lung vasculature
• capillaries of preterm mice remain deep within thickened septae, instead of aligning with the saccular epithelium, resulting in significantly fewer capillaries abutting saccular airspaces
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• severe with focal alveolar edema
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• impaired pulmonary angiogenesis
• occasionally exhibit misalignment of pulmonary veins, which are seen in anomalous locations adjacent to the lung pleura, running alongside arterial vessels and sharing a common adventitial sheath
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• E19.5 lungs show dramatic decrease of arteriolar branches and regions of marked capillary hypoperfusion
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• diastolic dimension is increased compared to in wild-type mice
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• membranous and muscular ventricular defects in 6 of 10 mice compared with 1 of 10 atrial septal defects in wild-type mice
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• in response to transverse aortic constriction (TAC)-induced pressure overload, wild-type hearts exhibit a progressive cardiac hypertrophy with significant dilatory remodeling whereas mutant hearts show more modest and concentric cardiac hypertrophy at 3 weeks, with minimal further progression
• at 9 weeks after TAC, mutant hearts develop significantly less intestitial fibrosis, myocyte hypertrophy, and fetal gene re-expression (B-natriuretic peptide and alpha-skeletal actin) relative wild-type hearts
• however, homozygotes show no significant differences in baseline heart weight or myocyte size relative to wild-type mice
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• high incidence (5 of 12) bicuspid aortic valves, however do not exhibit aortic coarctation
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• ventricular hypertrophy
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• after remnant kidney surgery, homozygotes develop microaneurysms unlike similarly-treated wild-type controls
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• E16 lungs show scattered areas of parenchymal and interlobar hemorrhages
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• at 9 weeks of TAC, wild-type hearts exhibit a rightward shift of LV pressure-volume (PV) loops and end-systolic and end-diastolic PV relations reflecting remodeling; in contrast, mutant hearts display a leftward shift with smaller end-diastolic and end-systolic chamber volumes, as well as preserved wall thickness and fractional shortening, indicating preserved or enhanced systolic and diastolic function
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• in fetal atrioventricular endothelial cushions, septum primum and right and left ventricular myocardium
• at E12.5, E15.5 and P1 in the myocardium
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• in response to TAC-induced pressure overload, homozygotes exhibit a similar or greater rise in LV systolic pressure and ventricular afterload (arterial elastance [Ea]) at 9 weeks relative to wild-type mice
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• at 2 months after right subcapsular nephrectomy and surgical resection of the poles of the left kidney to produce a remnant kidney (RK) model, homozygotes fail to exhibit a further increase in systolic blood pressure relative to sham-operated homozygotes, unlike wild-type controls
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respiratory system
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• E16 lungs show scattered areas of parenchymal and interlobar hemorrhages
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• fetal lungs demonstrate abnormally compact lung structure and lungs of pups show evidence of septal thickening and reduced airspaces
• E20 lungs display absence of discernible basement membrane in the distal airways
• exhibit a decrease in apoptosis in the lungs
• E16 lungs display scattered subpleural hematomas
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• abnormalities in pulmonary vascular development
• disorganization of the extracellular matrix structure in the lung vasculature
• capillaries of preterm mice remain deep within thickened septae, instead of aligning with the saccular epithelium, resulting in significantly fewer capillaries abutting saccular airspaces
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• severe with focal alveolar edema
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• observe an increase in markedly swollen glycogen laden pneumocytes protruding into airspaces compared to wild-type
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• no evidence of lamellar bodies in type II pneumocytes
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• pups exhibit marked septal thickening
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• some newborns exhibit severe respiratory distress
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• lack of surfactant in bronchial alveolar lavage fluid
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homeostasis/metabolism
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• after remnant kidney surgery, homozygotes exhibit a significantly higher increase in BUN levels relative to similarly-treated wild-type controls
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• serum osteocalcin (BGLAP) levels are significantly higher in sham treated compared to wild-type sham mice at baseline, 14 weeks and remain higher
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• serum TRAP5b (ACP5) concentrations are significantly higher in sham treated compared wild-type sham treated mice at all time points
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• after remnant kidney surgery, homozygotes exhibit a significantly higher increase in serum creatinine levels relative to similarly-treated wild-type controls
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• after remnant kidney surgery, homozygotes develop intraluminal thrombi unlike similarly-treated wild-type controls
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albuminuria
(
J:148626
)
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• after remnant kidney surgery, homozygotes exhibit a significantly higher increase in urinary albumin excretion relative to similarly-treated wild-type controls
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muscle
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• at 9 weeks of TAC, wild-type hearts exhibit a rightward shift of LV pressure-volume (PV) loops and end-systolic and end-diastolic PV relations reflecting remodeling; in contrast, mutant hearts display a leftward shift with smaller end-diastolic and end-systolic chamber volumes, as well as preserved wall thickness and fractional shortening, indicating preserved or enhanced systolic and diastolic function
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• in fetal atrioventricular endothelial cushions, septum primum and right and left ventricular myocardium
• at E12.5, E15.5 and P1 in the myocardium
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cellular
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• in fetal atrioventricular endothelial cushions, septum primum and right and left ventricular myocardium
• at E12.5, E15.5 and P1 in the myocardium
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• after remnant kidney surgery, homozygotes exhibit increased mesangial proliferation relative to similarly-treated wild-type controls
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• at 2 months after right subcapsular nephrectomy and surgical resection of the poles of the left kidney to produce a remnant kidney (RK) model, homozygotes exhibit a 4.6-fold increase in peritubular endothelial cell apoptosis relative to similarly-treated wild-type controls
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• in two week old mice based upon TUNEL staining and the presence of Apoptotic nuclei with a dense punctate appearance
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• after remnant kidney surgery, homozygotes exhibit a 36% reduction of proliferating endothelial cells in cortical peritubular capillaries relative to similarly-treated wild-type controls
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• serum osteocalcin (BGLAP) levels are significantly higher in sham compared wit wild-type sham mice at baseline and at 14 wk and remained higher
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• in response to TAC-induced pressure overload, homozygotes (but not wild-type mice) exhibit blunted myocardial ROS generation and blunted nitrotyrosine, and gelatinase zymogen activity with no significant decline in the GSH/GSSH or NADPH/NADP ratio
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endocrine/exocrine glands
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• on day 0.5 of estrous cycle, mutant ovaries display a scarce number of ovulation sites and a higher number of anovulatory and luteinized unruptured follicles relative to wild-type controls
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• on day 0.5 of estrous cycle, mutant ovaries exhibit significantly less corpora lutea than wild-type ovaries (9.7 +/- 1.2 versus 14.2 +/- 1.2, respectively)
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small ovary
(
J:145649
)
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• on day 0.5 of estrous cycle, mutant ovaries are significantly smaller than wild-type
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reproductive system
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• on day 0.5 of estrous cycle, mutant ovaries display a scarce number of ovulation sites and a higher number of anovulatory and luteinized unruptured follicles relative to wild-type controls
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• on day 0.5 of estrous cycle, mutant ovaries exhibit significantly less corpora lutea than wild-type ovaries (9.7 +/- 1.2 versus 14.2 +/- 1.2, respectively)
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small ovary
(
J:145649
)
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• on day 0.5 of estrous cycle, mutant ovaries are significantly smaller than wild-type
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anovulation
(
J:145649
)
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• female homozygotes display a higher rate of anovulation than wild-type controls (48.3 +/- 7.3% versus 29.7 +/- 6.3, respectively)
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• female homozygotes display a lower ovulation rate than wild-type controls (9.7 +/- 1.2% versus 14.2 +/- 1.2%, respectively)
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• mutant dams show a higher incidence of embryo losses than wild-type dams (62.5% versus 16.7%, respectively)
• the mean rate of embryo losses detected in mutant dams is 49.90.1% versus less than 20% in wild-type dams
• in mutant dams, the highest %s of embryo losses occur between days 8.5 and 10.5 (55.6%) and at day 13.5 postcoitum (44.4% of total losses), whereas in control dams embryo losses occur at days 10.5 and 11.5 postcoitum
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• on days 6.5 and 8.5 of pregnancy, the average number of embryos reaching implantation is lower in mutant mice relative to wild-type mice (4.0 +/- 0.4 versus 7.5 +/- 0.4, respectively)
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• on day 0.5 of estrous cycle, female homozygotes show a significant reduction in the total number of recovered embryos (oocytes/zygotes) relative to wild-type controls (4.0 +/- 1.1 versus 10.4 +/- 1.6, respectively)
• thereafter, a mean of 2.0 +/- 1.0 of these recovered embryos are found to be fertilized, representing a non-fertilization rate of 50.7% versus only 3.3% in control littermates
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immune system
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• serum concentrations of TRAP5b (ACP5) are significantly higher in sham treated compared to wild-type sham treated mice at all time points
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• fever in response to turpentine injection is enhanced compared to wild-type controls
• unlike in mice null for either Nos1 or Nos2, fever in response to LPS injection is not significantly different from wild-type controls
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• after remnant kidney surgery, homozygotes exhibit increased macrophage infiltration in the glomeruli (15.4-fold) and in the tubulointerstitium (2.7-fold) relative to similarly-treated wild-type controls
• however, a similar increase in glomerular T-cell infiltration (62%) is seen in both RK groups
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renal/urinary system
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• at 2 months after right subcapsular nephrectomy and surgical resection of the poles of the left kidney to produce a remnant kidney (RK) model, homozygotes exhibit a 4.6-fold increase in peritubular endothelial cell apoptosis relative to similarly-treated wild-type controls
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• in two week old mice based upon TUNEL staining and the presence of Apoptotic nuclei with a dense punctate appearance
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• after remnant kidney surgery, homozygotes exhibit a 36% reduction of proliferating endothelial cells in cortical peritubular capillaries relative to similarly-treated wild-type controls
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albuminuria
(
J:148626
)
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• after remnant kidney surgery, homozygotes exhibit a significantly higher increase in urinary albumin excretion relative to similarly-treated wild-type controls
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• after remnant kidney surgery, homozygotes exhibit increased macrophage infiltration in the glomeruli (15.4-fold) and in the tubulointerstitium (2.7-fold) relative to similarly-treated wild-type controls
• however, a similar increase in glomerular T-cell infiltration (62%) is seen in both RK groups
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• in 80% of adult freshly isolated kidneys indentations are observed, indicating zones of parenchymal scarring
• 4% of glomeruli outside scarred area exhibit loss of cellularity and vasculature, a hyalinization like appearance
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• after remnant kidney surgery, homozygotes exhibit a 44% increase in tubulointerstitial injury relative to similarly-treated wild-type controls
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• glomeruli within scarred areas are considerably smaller than wild-type
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• after remnant kidney surgery, homozygotes exhibit a significantly greater endothelial cell loss than similarly-treated wild-type controls
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• after remnant kidney surgery, homozygotes exhibit increased mesangial proliferation relative to similarly-treated wild-type controls
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• after remnant kidney surgery, homozygotes exhibit increased matrix deposition in some glomeruli unlike similarly-treated wild-type controls
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• after remnant kidney surgery, homozygotes develop mesangiolysis unlike similarly-treated wild-type controls
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• within scarred areas
(J:117046)
• after remnant kidney surgery, homozygotes develop significant glomerulosclerosis, unlike similarly-treated wild-type controls
(J:148626)
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• after remnant kidney surgery, homozygotes exhibit a 46% increase in glomerular collagen IV deposition relative to similarly-treated wild-type controls
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• after remnant kidney surgery, homozygotes develop significantly greater glomerular hypertrophy than similarly-treated wild-type controls
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• frequently a large lipid droplet is observed with Bowman's capsule and the adjacent matrix
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• after remnant kidney surgery, homozygotes exhibit more severe sloughing , vacuolization and nuclear exfoliation of tubular epithelial cells relative to similarly-treated wild-type controls
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• thin strands of connective tissue distributed loosely within the interglomerular interstitium
(J:117046)
• after remnant kidney surgery, homozygotes exhibit a 38% increase in collagen III deposition in the tubulointerstitium relative to similarly-treated wild-type controls
(J:148626)
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• within scarred areas
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• the glomeruli often display no clear connection to typical large-diameter proximal tubules
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• after remnant kidney surgery, homozygotes exhibit more severe tubular dilatation than similarly-treated wild-type controls
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• in 2 week old mice, as pyknotic nuclei and vacuolated cytoplasm are observed
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renal cast
(
J:148626
)
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• after remnant kidney surgery, homozygotes exhibit more severe tubular cast formation than similarly-treated wild-type controls
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• degeneration of the glomerular core components is common within the scarred zones
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• after remnant kidney surgery, homozygotes exhibit significantly worse renal function relative to similarly-treated wild-type controls
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skeleton
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• serum osteocalcin (BGLAP) levels are significantly higher in sham compared wit wild-type sham mice at baseline and at 14 wk and remained higher
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• serum concentrations of TRAP5b (ACP5) are significantly higher in sham treated compared to wild-type sham treated mice at all time points
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• exagerated BMD decrease in ovariectomized mice
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• between 10-20 weeks post sham-operation compared to sham-operated wild-type
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• significantly greater cortical thickness in sham operated mice compared to sham operated wild-type mice
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hematopoietic system
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• serum concentrations of TRAP5b (ACP5) are significantly higher in sham treated compared to wild-type sham treated mice at all time points
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| aortic valve disease | DOID:62 | J:103340 | ||
| persistent fetal circulation syndrome | DOID:13042 |
OMIM:265380 |
J:98913 | |
