Analysis Tools
integument
| N |
• no calcification occurs in the fibrous capsule surrounding the muzzle vibrissae
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Allele Symbol Allele Name Allele ID |
Tg(Cdh16-cre)91Igr transgene insertion 91, Peter Igarashi MGI:2665300 |
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| Summary |
52 genotypes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• no calcification occurs in the fibrous capsule surrounding the muzzle vibrissae
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• renal function and renal interstitial fibrosis are improved compared to conditional Pkd1 compound heterozygotes and mice live past 1 year of age
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• mice show a decrease in cyst epithelial cell proliferation compared to conditional Pkd1 compound heterozygotes
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• cyst size is reduced compared to conditional Pkd1 compound heterozygotes
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• kidney weight is reduced compared to conditional Pkd1 compound heterozygotes
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• the number of peroxisomes in the kidneys is reduced compared to conditional Pkd1 compound heterozygotes
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• mice show a decrease in cyst epithelial cell proliferation compared to conditional Pkd1 compound heterozygotes
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• fatty acid oxidation is increased in kidneys compared to conditional Pkd1 compound heterozygotes
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• reactive oxidative species level is decreased in the kidneys compared to conditional Pkd1 compound heterozygotes
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• fatty acid oxidation is increased in kidneys compared to conditional Pkd1 compound heterozygotes
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• mice show decreased levels at 3, 7, and 15 weeks of age compared to conditional Pkd1 compound heterozygotes
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• cyst size is reduced compared to conditional Pkd1 compound heterozygotes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• median survival is 206 days
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• mice develop polycystic kidney disease
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• mice show impaired renal function
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• increase in cyst epithelial cell proliferation
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• the number of peroxisomes is decreased in kidney cysts
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• increase in cyst epithelial cell proliferation
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• fatty acid oxidation is decreased in kidneys
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• reactive oxidative species level is increased in the kidneys
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• fatty acid oxidation is decreased in kidneys
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• levels are increased at 3, 7, and 15 weeks of age
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• mice develop polycystic kidney disease
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| polycystic kidney disease 1 | DOID:0110858 |
OMIM:173900 |
J:244067 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice exhibit attenuated cyst growth and reduced renal fibrosis compared to single Pkd1tm1.1Pcha homozygotes
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• mice exhibit lower blood urea nitrogen (BUN) levels compared to single Pkd1tm1.1Pcha homozygotes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• more severe than in Prkcshtm1Som/Prkcshtm1Som Tg(Cdh16-cre)91Igr mice
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• more severe than in Prkcshtm1Som/Prkcshtm1Som Tg(Cdh16-cre)91Igr mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• increased apoptosis in cysts compared to in cysts from Prkcshtm1Som/Prkcshtm1Som Tg(Cdh16-cre)91Igr mice
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• increased cell proliferation in cysts compared to in cysts from Prkcshtm1Som/Prkcshtm1Som Tg(Cdh16-cre)91Igr mice
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• more severe than in Prkcshtm1Som/Prkcshtm1Som Tg(Cdh16-cre)91Igr mice
• collecting ducts form larger cysts than in Prkcshtm1Som/Prkcshtm1Som Tg(Cdh16-cre)91Igr mice
• cysts exhibit increased proliferation and apoptosis compared with cysts from Prkcshtm1Som/Prkcshtm1Som Tg(Cdh16-cre)91Igr mice
• expression Tg(Pkd2)#Som expression does not rescue cystic kidney phenotype
• however, expression of Tg(Pdk1)248Som or treatment with carfilzomib rescues cystic kidney phenotype
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• dilated to a lesser extent than collecting tubules
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• increased apoptosis in cysts compared to in cysts from Prkcshtm1Som/Prkcshtm1Som Tg(Cdh16-cre)91Igr mice
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• increased cell proliferation in cysts compared to in cysts from Prkcshtm1Som/Prkcshtm1Som Tg(Cdh16-cre)91Igr mice
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• more severe than in Prkcshtm1Som/Prkcshtm1Som Tg(Cdh16-cre)91Igr mice
• collecting ducts form larger cysts than in Prkcshtm1Som/Prkcshtm1Som Tg(Cdh16-cre)91Igr mice
• cysts exhibit increased proliferation and apoptosis compared with cysts from Prkcshtm1Som/Prkcshtm1Som Tg(Cdh16-cre)91Igr mice
• expression Tg(Pkd2)#Som expression does not rescue cystic kidney phenotype
• however, expression of Tg(Pdk1)248Som or treatment with carfilzomib rescues cystic kidney phenotype
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• increased apoptosis in cysts compared to in cysts from Sec63tm1Som/Sec63tm1Som Tg(Cdh16-cre)91Igr mice
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• increased cell proliferation in cysts compared to in cysts from Sec63tm1Som/Sec63tm1Som Tg(Cdh16-cre)91Igr mice
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• more severe than in Sec63tm1Som/Sec63tm1Som Tg(Cdh16-cre)91Igr mice
• collecting duct forms larger cysts than in Sec63tm1Som/Sec63tm1Som Tg(Cdh16-cre)91Igr mice
• cysts exhibit increased proliferation and apoptosis compared with cysts from Prkcshtm1Som/Prkcshtm1Som Tg(Cdh16-cre)91Igr mice
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• dilated to a lesser extent than collecting tubules
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• increased apoptosis in cysts compared to in cysts from Sec63tm1Som/Sec63tm1Som Tg(Cdh16-cre)91Igr mice
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• increased cell proliferation in cysts compared to in cysts from Sec63tm1Som/Sec63tm1Som Tg(Cdh16-cre)91Igr mice
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• more severe than in Sec63tm1Som/Sec63tm1Som Tg(Cdh16-cre)91Igr mice
• collecting duct forms larger cysts than in Sec63tm1Som/Sec63tm1Som Tg(Cdh16-cre)91Igr mice
• cysts exhibit increased proliferation and apoptosis compared with cysts from Prkcshtm1Som/Prkcshtm1Som Tg(Cdh16-cre)91Igr mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mild at 6 months
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• mild at 6 months
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• mild at 6 months
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mild at P45
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• mild at P45
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• more severe than in either single conditional knock-outs
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• more severe than in either single conditional knock-outs
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• by P60 associated with kidney cysts
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• mild at P14, advanced at P30 and severe at P69
• collecting ducts form large cysts
• however, expression of Tg(Pdk1)248Som slows development of cystic kidney phenotype
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• dilated to a lesser extent than collecting tubules
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• mild at P14, advanced at P30 and severe at P69
• collecting ducts form large cysts
• however, expression of Tg(Pdk1)248Som slows development of cystic kidney phenotype
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• by 6 months associated with kidney cysts
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• mild at P28, advanced at 3 months and severe at 6 months
• collecting ducts form large cysts
• expression Tg(Pkd2)#Som expression does not rescue cystic kidney phenotype
• however, expression of Tg(Pdk1)248Som slows development of cystic kidney phenotype
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• dilated to a lesser extent than collecting tubules
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• mild at P28, advanced at 3 months and severe at 6 months
• collecting ducts form large cysts
• expression Tg(Pkd2)#Som expression does not rescue cystic kidney phenotype
• however, expression of Tg(Pdk1)248Som slows development of cystic kidney phenotype
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice do not exhibit any characteristic BBS phenotypes such as obesity or retinal degeneration and show no detectable defects in renal morphology or function up to 3 months of age
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
 |
• adenocarcinomas (serous and clear cell) show KPNA2 expression while endometrial intraepithelial carcinomas and endometrial glandular dysplasia foci do not exhibit KPNA2 overexpression
(J:214850)
• mice show endometrial alterations that progress from normal epithelium to endometrial glandular dysplasia, to endometrial intraepithelial carcinoma, and finally to a papillary adenocarcinoma
(J:215149)
• 16 of 19 females at 65-67 weeks of age develop endometrial tumors; three different histological subtypes of type II endometrial carcinomas, as well as carcinosarcomas, develop at high frequency
(J:215149)
• individual mice frequently exhibit multiple independent endometrial tumors of different histological appearances
(J:215149)
• adenocarcinomas with a papillary growth pattern form exclusively from the surface epithelium of the lumen, whereas those with an acinar growth pattern arise from endometrial glands; both are either serous or clear cell adenocarcinomas
(J:215149)
• an intermediate lesion, microinvasive adenocarcinoma, is seen in the glandular compartment of the endometrium
(J:215149)
• the lumen surface epithelium also shows sites of endometrial intraepithelial carcinoma with papillary structures lesion characterized by a papillary growth pattern with fibrovascular core
(J:215149)
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• all mice at 24-29 weeks of age show some regions of endometrial glandular dysplasia which are characterized by enlarged and hyperchromatic nuclei, prominent nucleoli, nuclear crowding and loss of basal nuclear localization
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• regions of the epithelium of the corpus epididymis of males frequently develop a vacuolated appearance and display nuclear atypia at around 6 months of age; these lesions do not progress to tumors
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• adenocarcinomas (serous and clear cell) show KPNA2 expression while endometrial intraepithelial carcinomas and endometrial glandular dysplasia foci do not exhibit KPNA2 overexpression
(J:214850)
• mice show endometrial alterations that progress from normal epithelium to endometrial glandular dysplasia, to endometrial intraepithelial carcinoma, and finally to a papillary adenocarcinoma
(J:215149)
• 16 of 19 females at 65-67 weeks of age develop endometrial tumors; three different histological subtypes of type II endometrial carcinomas, as well as carcinosarcomas, develop at high frequency
(J:215149)
• individual mice frequently exhibit multiple independent endometrial tumors of different histological appearances
(J:215149)
• adenocarcinomas with a papillary growth pattern form exclusively from the surface epithelium of the lumen, whereas those with an acinar growth pattern arise from endometrial glands; both are either serous or clear cell adenocarcinomas
(J:215149)
• an intermediate lesion, microinvasive adenocarcinoma, is seen in the glandular compartment of the endometrium
(J:215149)
• the lumen surface epithelium also shows sites of endometrial intraepithelial carcinoma with papillary structures lesion characterized by a papillary growth pattern with fibrovascular core
(J:215149)
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| endometrial cancer | DOID:1380 |
OMIM:608089 |
J:214850 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• no kidney pathology is seen in mice induced with doxycycline
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• increase in fractional excretion of potassium on both a normal chow and low potassium diet
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• elevated urine sodium excretion after 2 - 4 days on a low sodium diet compared to diet matched wild-type controls
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• ambient osmolarity of spot urine is significantly reduced
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• blunted diuretic response to furosemide
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• on both a normal chow and low potassium diet
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• increase in fractional excretion of potassium on both a normal chow and low potassium diet
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• elevated urine sodium excretion after 2 - 4 days on a low sodium diet compared to diet matched wild-type controls
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• ambient osmolarity of spot urine is significantly reduced
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• mice on a low sodium diet but not mice on a normal chow diet develop relative systolic hypotension
• however, on a normal chow diet blood pressure is normal
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
Polycystic kideny disease in Kif3atm1Gsn/Kif3atm2Gsn Tg(Cdh16-cre)91Igr/0 mutant mice
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• mutant kidneys contain multiple, fluid-filled cysts in both the cortex and medulla
• cysts are first noted at P5 as fusiform dilatations of the collecting ducts in the renal medulla
• cyst epithelial cells lack primary cilia and display altered cell polarity as well as increased proliferation and apoptosis
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• cysts are first noted at P5 as fusiform dilatations of the collecting ducts in the renal medulla
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• by P35, the renal parenchyma is entirely replaced with multiple, large fluid-filled cysts
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• mice display growth retardation by P35
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• at P28, mutant kidneys are grossly enlarged
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• cilia are present in neonatal collecting ducts prior to the onset of cyst formation (P5), but are lost during postnatal development
• mice lack tubulin-positive cilia on the luminal surfaces of most cyst epithelial cells derived from the loops of Henle and collecting ducts
• cilia are missing from the surface of epithelial cells lining the cysts but are present in adjacent noncystic tubules
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• cyst epithelial cells display increased apoptosis
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• mutant kidneys contain multiple, fluid-filled cysts in both the cortex and medulla
• cysts are first noted at P5 as fusiform dilatations of the collecting ducts in the renal medulla
• cyst epithelial cells lack primary cilia and display altered cell polarity as well as increased proliferation and apoptosis
|
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• cysts are first noted at P5 as fusiform dilatations of the collecting ducts in the renal medulla
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• by P35, the renal parenchyma is entirely replaced with multiple, large fluid-filled cysts
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• at P28, mutant kidneys are grossly enlarged
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• advanced kidney cysts are surrounded by areas of interstitial fibrosis
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• advanced kidney cysts are surrounded by atrophic tubules
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• mice exhibit renal failure by P21
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• mice exhibit a rapid increase in BUN levels after P14
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• cilia are present in neonatal collecting ducts prior to the onset of cyst formation (P5), but are lost during postnatal development
• mice lack tubulin-positive cilia on the luminal surfaces of most cyst epithelial cells derived from the loops of Henle and collecting ducts
• cilia are missing from the surface of epithelial cells lining the cysts but are present in adjacent noncystic tubules
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• cyst epithelial cells display increased apoptosis
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| polycystic kidney disease | DOID:0080322 |
OMIM:PS173900 |
J:83293 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mutants do not develop hydronephrosis
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• hyperproliferation and enlarged epithelial cells in the ureter
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• hyperproliferation and enlarged epithelial cells in the bladder
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• hydronephrosis, characterized by an expansion of the renal pelvis
• however, mutants do not display histological abnormalities in the urothelium of the renal pelvis or ureter, or in the structure of the tubules in the kidney cortex or medulla
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• cysts exhibit a 3- to 6-fold increase in the number of Ki-67-positive kidney epithelial cells per mm2 of cortex
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• mutants develop multiple epithelial tubule cysts in the kidney cortex and medulla
• cysts develop in all mice (14 of 14) and are seen as early as 6-8 weeks of age
• cysts arise in collecting ducts and distal tubules
• most cysts are lined by a single layer of epithelial cells (simple cysts), whereas ~8% of cysts are lined by multilayered epithelial cells with
occasional papillary projections (atypical cysts)
• mutants exhibit reduced frequency of primary cilia in cysts, with distal tubule cysts displaying only ~30% ciliated cells relative to 80-90% ciliated cells in wild-type
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• mutants develop multiple epithelial tubule cysts in the kidney cortex
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• mutants develop multiple epithelial tubule cysts in the kidney medulla
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• males and females exhibit enlarged and heavier kidneys due to epithelial tubule cysts
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• 3 of 14 mice show isolated regions of benign squamous metaplasia within the kidney cortex
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• kidney epithelial cells fail to maintain their primary cilia, resulting in uncontrolled proliferation and cyst formation
|
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• mutants exhibit reduced frequency of primary cilia in cysts, with distal tubule cysts displaying only ~30% ciliated cells relative to 80-90% ciliated cells in wild-type
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• hyperproliferation of the urothelium in the renal pelvis is more pronounced than in single Pten mutants
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• mutants exhibit reduced frequency of primary cilia in cysts, with distal tubule cysts displaying only ~30% ciliated cells relative to 80-90% ciliated cells in wild-type
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• cysts exhibit a 3- to 6-fold increase in the number of Ki-67-positive kidney epithelial cells per mm2 of cortex
|
| N |
• no tumors areas seen at 3-6 months of age, when mice are euthanized to avoid renal failure
|
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• mutants develop multiple epithelial tubule cysts in the kidney cortex and medulla
• cysts develop in all mice (14 of 14) and are seen as early as 6-8 weeks of age
• cysts arise in collecting ducts and distal tubules
• most cysts are lined by a single layer of epithelial cells (simple cysts), whereas ~8% of cysts are lined by multilayered epithelial cells with
occasional papillary projections (atypical cysts)
• mutants exhibit reduced frequency of primary cilia in cysts, with distal tubule cysts displaying only ~30% ciliated cells relative to 80-90% ciliated cells in wild-type
|
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• mutants develop multiple epithelial tubule cysts in the kidney cortex
|
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• mutants develop multiple epithelial tubule cysts in the kidney medulla
|
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• males and females exhibit enlarged and heavier kidneys due to epithelial tubule cysts
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| von Hippel-Lindau disease | DOID:14175 |
OMIM:193300 |
J:137073 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice exhibit a median survival of 21 days which is a 50% improvement compared to single Pkd1 conditional mutants
|
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• the number of proliferating cyst epithelial cells is reduced by 78.7% compared to single Pkd1 conditional mutants
|
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• mice exhibit a 26.8% reduction in kidney-weight-to-body-weight ratio compared to single Pkd1 conditional mutants
|
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• the number of proliferating cyst epithelial cells is reduced by 78.7% compared to single Pkd1 conditional mutants
|
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• mice exhibit a 22% reduction in serum creatinine levels compared to single Pkd1 conditional mutants
|
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|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• median survival is 14 days, with mice starting to die around 10 days and most die by 20 days of age
|
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• increase in cyst epithelial cell proliferation
|
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• mice develop an early-onset and rapidly fatal form of polycystic kidney disease
|
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• increase in cyst epithelial cell proliferation
|
|
• mice develop an early-onset and rapidly fatal form of polycystic kidney disease
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| polycystic kidney disease 1 | DOID:0110858 |
OMIM:173900 |
J:244067 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• rare mice that survive to adulthood become moribund at 8-12 weeks of age
|
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• most mice die within 2-3 days of birth
• only 6 of 540 mice survive to weaning age
|
|
• multiple kidney cysts are already noted at P2, involving both the nephrogenic zone and renal cortex
• at 8 weeks of age, kidney cysts include simple cysts lined by a single layer of epithelial cells, glomerular cysts, and multilayered cysts lined by a hyperplastic epithelium
• Ki67 staining revealed a dramatic increase in proliferation in the cyst wall epithelium
• kidney cysts are derived from multiple cell types including Bowman's capsule, proximal tubules, thick ascending limbs, distal convoluted tubules, and collecting ducts
• multilayered hyperplastic cysts display characteristics of neoplasia
• no loss of cilia in renal tubular epithelia is observed; however, large multilayered cysts show complete lack of cilia
|
|
• at 8 weeks of age, 6 of 6 mice display severe polycystic kidney disease
|
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• at 8 weeks of age, kidneys are severely enlarged
|
|
• at 8 weeks of age, at least 2 of 6 mice show clear evidence of cystic renal adenoma
• however, no evidence of metastatic disease is observed in adult mice
|
|
• rare mice that survive to adulthood weigh 3-4 grams less than control littermates
|
|
• multiple kidney cysts are already noted at P2, involving both the nephrogenic zone and renal cortex
• at 8 weeks of age, kidney cysts include simple cysts lined by a single layer of epithelial cells, glomerular cysts, and multilayered cysts lined by a hyperplastic epithelium
• Ki67 staining revealed a dramatic increase in proliferation in the cyst wall epithelium
• kidney cysts are derived from multiple cell types including Bowman's capsule, proximal tubules, thick ascending limbs, distal convoluted tubules, and collecting ducts
• multilayered hyperplastic cysts display characteristics of neoplasia
• no loss of cilia in renal tubular epithelia is observed; however, large multilayered cysts show complete lack of cilia
|
|
• at 8 weeks of age, 6 of 6 mice display severe polycystic kidney disease
|
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• at 8 weeks of age, kidneys are severely enlarged
|
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• BUN levels are significantly increased in early postnatal period (P2)
• BUN levels are also significantly increased in the rare mice that survive to adulthood
|
|
• at 8 weeks of age, at least 2 of 6 mice show clear evidence of cystic renal adenoma
• however, no evidence of metastatic disease is observed in adult mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• tumors contain regions of cystadenoma characterized by adenoid structures identical to human cystadenoma lesions arising in epididymides
• cystadenoma display clear cell morphology
|
|
|
• cysts and squamous epithelial hyperplasia in the oviduct
|
|
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• females exhibit hyperplasia and full squamous differentiation of the uterine endometrial lumen, endometrial hyperplasia, and endometrial hyperplasia with cyst formation
|
|
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• cysts and squamous epithelial hyperplasia in the cervix
|
|
|
• squamous metaplasia is seen in the epididymis
• vascularization is increased in the epididymides
|
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• regions of squamous differentiation intermingle with the regions of cystadenoma
• cystadenomas appear to result from basal cell proliferation without differentiation, whereas regions of squamous metaplasia contain abundant basal cells in basal layers as well as cells with markers of epidermal differentiation
|
|
• all mutants develop benign mixed adenosquamous genital tract tumors (in epididymis, vesicular glands, vas deferens, endometrium, and oviduct) resembling clear cell cystadenomas that form in patients with Von Hippel-Lindau syndrome (VHL)
• tumors arise simultaneously in all genital tract epithelia and show expansion of basal cells
• endometrial hyperplasia with cyst formation resembles cystadenoma and cystic lesions seen in broad ligament of females with VHL
|
|
|
• tumors contain regions of cystadenoma characterized by adenoid structures identical to human cystadenoma lesions arising in epididymides
• cystadenoma display clear cell morphology
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| von Hippel-Lindau disease | DOID:14175 |
OMIM:193300 |
J:137442 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• aberrant presence of dilated blood capillaries surrounding epididymal tubules indicating increased vascularization
• however, the genital tracts of males and females look normal
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• epithelial hyperplasia in vesicular glands
|
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• genital tissues are enlarged
|
|
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• epithelial hyperplasia in vesicular glands
|
|
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• endometrial hyperplasia is accompanied by partial squamous differentiation
|
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• hyperplasia of the endometrial glands and lumen
|
|
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• epithelial hyperplasia in epididymis
|
|
|
• epithelial hyperplasia in vas deferens
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• die of kidney failure by 3 weeks of age
• in late stages degeneration, necrosis and hemorrhages are seen
• rapamycin treatment extends survival with some mice surviving more than 50 days
|
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• seen in late stages of kidney failure
|
|
• develop bilateral polycystic kidneys
|
|
• kidney weight is increased 10 fold compared to controls
|
|
• hyperplasia and renal cell carcinoma are seen by P18
• cystic renal cell carcinoma is frequently seen in extremely enlarged kidneys
|
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• extremely dilated tubules, predominantly originating from the collecting ducts
|
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• atrophic, compressed glomeruli are seen
|
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• hyperplastic areas with multiple layers of epithelial cells are seen along the inner surface of tubules
|
|
• some proximal tubules are highly to moderately dilated
|
|
• by 3 weeks of age
|
|
• levels of blood urea nitrogen are increased over 10 fold compared to littermate controls
|
|
• hyperplasia and renal cell carcinoma are seen by P18
• cystic renal cell carcinoma is frequently seen in extremely enlarged kidneys
|
|
• seen in late stages of kidney failure
|
|
• develop bilateral polycystic kidneys
|
|
• kidney weight is increased 10 fold compared to controls
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| Birt-Hogg-Dube syndrome | DOID:0050676 |
OMIM:135150 |
J:143922 | |
| nonpapillary renal cell carcinoma | DOID:0050387 |
OMIM:144700 |
J:143922 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• nearly all mice die 6 to 14 hours after birth due to urinary obstruction
• however, a few mice survive past the first day
|
| N |
• no apoptosis is detected in collecting duct epithelia
|
|
• severe bilateral in dead newborn mice
(J:226950)
• however, mice that survive beyond the first day do not exhibit hydronephrosis
(J:226950)
|
|
• along the nephron, including at the tips of branching ureteric buds
• most severe dilation is found in the distal sections of the nephron
|
|
• uroplakin plaques are completely missing on the luminal surface of E17.5 ureters
|
|
• increased proliferation rates by E17.5
|
|
• absence of lumen in obstructed ureters with rampant overgrowth of mesenchymal-shaped cells that may be either smooth muscle cells or myofibroblasts
(J:226950)
• urothelial layer at E16.5 shows a reduction in apical microvilli
(J:250161)
• E17.5 ureters show an abnormal single urothelial layer rather than a two-layered urothelium, with gaps in the epithelium and cells pulling away from the basement membrane toward the center of the lumen
(J:250161)
• urothelial cells at E17.5 have lost large amounts of cytoplasm, and show irregular disrupted plasma membranes and unusual distributions of electron-dense material in the nuclei
(J:250161)
• at E17.5, but not E16.5, the urothelial layer is about half the width or control urothelium
(J:250161)
• ureters show a complete loss of the epithelial layer at E18.5, indicating urothelial degeneration
(J:250161)
• urothelial cells do not show tight cell-cell contacts at E17.5
(J:250161)
• ureters at E17.5 show a complete absence of intracellular vesicles in the apical membrane of the superficial urothelial cells
(J:250161)
• urothelial cells in the developing ureter die largely due to necrosis and not apoptosis
(J:250161)
• however, no changes in the width of the smooth muscle layer are seen at E16.5 or E17.5
(J:250161)
|
|
• develops between E16.5 and E18.5
(J:226950)
• at E18.5 and in newborn mice with deposits of white debris
(J:226950)
• mice develop bilateral in utero ureteropelvic junction obstructions, with granulation tissue filling the ureter lumen
(J:250161)
• obstructed ureters exhibit stromal remodeling, with the lumen filled with fibroblastic cells and extracellular matrix deposits
(J:250161)
|
|
• increased smooth muscle proliferation rates by E17.5
(J:226950)
• urothelial barrier is compromised in the E17.5 ureter becoming leaky to luminal fluid
(J:250161)
|
|
• heart distention in mice that die after birth
|
|
• in mice that die after birth
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| obstructive nephropathy | DOID:0070314 | J:250161 , J:226950 | ||
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• urea cycle metabolism is rescued
|
| N |
• kidney size and morphology are rescued
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• urea cycle metabolism is rescued
|
| N |
• kidney size and morphology are rescued
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• at 8 to 12 weeks
|
|
• at 8 to 12 weeks
|
|
• at 8 to 12 weeks
|
|
• at P1
• however, this difference faded as animals age
|
|
• macro-albuminuria
|
|
• proximal tubular epithelial (PTE) cells exhibit accumulation of intracellular endosomal vesicles unlike in wild-type cells
• PTE cells are more hyperpolarized and acidic with decreased albumin uptake compared with wild-type cells
|
|
• at 8 to 12 weeks
|
|
• at 8 to 12 weeks
|
|
• at 8 to 12 weeks
|
|
• at 8 to 12 weeks
|
|
• at 8 to 12 weeks
|
|
• at P1
• however, this difference faded as animals age
|
|
• macro-albuminuria
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• all animals exhibit macroscopic renal cysts at post-mortem;
(J:120969)
• some cells lining the cysts show poor intercellular cohesion and mild nuclear variation
(J:120969)
• cysts are derived from ascending limb of the Loop of Henle and from collecting ducts
(J:120969)
|
|
• at cortico-medullary junction, kidneys display extensive cytic changes; these irregular cysts are lined with cuboidal epithelium
|
|
• mice accumulate fumarate, argininosuccinate and citrulline in the kidneys whereas aspartate is depleted
|
|
• cysts occasionally show lack of cytochrome c oxidase activity
|
|
• all animals exhibit macroscopic renal cysts at post-mortem;
(J:120969)
• some cells lining the cysts show poor intercellular cohesion and mild nuclear variation
(J:120969)
• cysts are derived from ascending limb of the Loop of Henle and from collecting ducts
(J:120969)
|
|
• at cortico-medullary junction, kidneys display extensive cytic changes; these irregular cysts are lined with cuboidal epithelium
|
|
• mice accumulate fumarate, argininosuccinate and citrulline in the kidneys whereas aspartate is depleted
|
|
• occasionally sclerotic glomeruli are seen in tubules
|
|
• some tubules are lined by vacuolated epithelium containing proteinaceous debris, but most have small amounts of eosinophilic secretion
|
|
• mild hydronephrosis is seen in mice >14 months old
|
|
• some mice develop polyuric renal failure at 8 months of age
|
|
• in mouse embryonic fibroblasts
|
|
• mouse embryonic fibroblasts exhibit multiple defects in the Krebs cycle and utilizes the urea cycle but not reductive carboxylation compared with wild-type cells
• mouse embryonic fibroblasts exhibit increased sensitivity to arginine deprivation with reduced colony growth and survival compared with wild-type cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• most mice die between P30 and P45 with no mice surviving past P60
|
|
• delayed compared to in Wnt9btm1Amc homozygotes
• few cysts at P1
• prevalent by P10
• by P15, mice develop cysts in all nephrons of glomerulus, proximal tubule, loop of Henle and collecting duct
|
|
• collecting duct epithelial cells exhibit randomized elongation unlike in wild-type mice
|
|
• at P5, epithelium cell divisions are not oriented within the plane of the epithelium unlike in control mice
• by P30, little normal epithelia remains
|
|
• delayed compared to in Wnt9btm1Amc homozygotes
• few cysts at P1
• prevalent by P10
• by P15, mice develop cysts in all nephrons of glomerulus, proximal tubule, loop of Henle and collecting duct
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• cystic index at P1 is increased compared to in Wnt9btm1.1Amc/Wnt9btm1.2Amc Tg(Cdh16-cre)91Igr mice
|
|
• cystic index at P1 is increased compared to in Wnt9btm1.1Amc/Wnt9btm1.2Amc Tg(Cdh16-cre)91Igr mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice die by P2
|
|
• mild at birth
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice exhibit no overt survival difference up to ~22 months of age relative to controls
|
|
• at 8 weeks of age, mice exhibit a significantly smaller body weight relative to controls
• however, no significant differences in the weight of vital organs (kidney, liver, heart and lungs) are observed
|
| N |
• mice exhibit no overt decrease in renal function, as measured by serum creatinine levels
|
|
• mice show prominent epithelial cell swelling in the dilated distal tubules
|
|
• mice exhibit dilated distal tubules within the cortex region relative to controls
|
|
• dilated distal tubules show a significant increase in proteinacious casts within the tubular lumen
• acellular casts within distal tubules, collecting ducts, and Loops of Henle display positive staining for tyrosine nitration
|
|
• mice display a significant increase in oxidative stress (tyrosine nitration) in dilated renal tubules
• tyrosine nitration is detected in cortical regions (dilated distal tubules and collecting ducts) as well as medullary regions (including the collecting ducts and Loops of Henle)
|
| N |
• mice exhibit normal blood glucose levels relative to controls
• no significant difference in serum creatinine levels relative to controls
|
| N |
• mice exhibit no significant change in systolic blood pressure relative to controls
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice show prominent epithelial cell swelling in the dilated distal tubules
|
|
• mice display a significant increase in oxidative stress (tyrosine nitration) in dilated renal tubules
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• treatment of mice with rapamycin extends lifespan nearly 2-fold, but all animals die of renal failure
|
|
• animals appear normal at birth, but develop distended abdomens and die around 3 weeks of age from renal failure
|
|
• at 3 weeks, kidneys are markedly cystic
|
|
• by 2 weeks, mice display distended abdomens which are very pronounced at time of death
|
|
• at time of death, enlarged kidneys fill abdominal cavity; penetrance of phenotype is 100%
• enlargement begins at 1 week due to collecting duct dilation
|
|
• between P7 and P21, kidney to body weight ratio (under wet and dried conditions) dramatically increases relative to littermate controls
|
|
• kidneys have fine reticular pattern of interstitial tissue containing numerous blood vessels, not observed in control kidneys
|
|
• in culture, tubule cells show much higher proliferation rate than control cells
|
|
• at 3 weeks, kidneys are markedly cystic
|
|
• at time of death, enlarged kidneys fill abdominal cavity; penetrance of phenotype is 100%
• enlargement begins at 1 week due to collecting duct dilation
|
|
• between P7 and P21, kidney to body weight ratio (under wet and dried conditions) dramatically increases relative to littermate controls
|
|
• by 2 weeks, lumens of ducts are cystic
• at 3 weeks, collecting ducts in the medulla and extending into the papilla are severely cystic
|
|
• by 1 week of age, dilation of collecting ducts is observed
|
|
• anatomical distinction between cortex and medulla is disrupted
|
|
• regions of pyramidal infarctions are observed at 3 weeks
|
|
• by 2 weeks, lumens of tubules are cystic
• most cells lining the tubules are hypertrophic with enlarged nuclei and cytoplasm; many cells ar hyperplastic
|
|
• by 2 weeks, lumens of tubules are cystic
|
|
• occurs around 3 weeks of age
|
|
• kidneys have fine reticular pattern of interstitial tissue containing numerous blood vessels, not observed in control kidneys
|
|
• levels are significantly elevated at 2 and 3 weeks of age, compared to controls
|
|
• in culture, tubule cells show much higher proliferation rate than control cells
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| Birt-Hogg-Dube syndrome | DOID:0050676 |
OMIM:135150 |
J:130978 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• no increase in severity of cystic phenotype compared to mutant mice wild-type for Flcn
|
|
• no increase in severity of phenotype compared to mutant mice wild-type for Flcn
|
|
• no increase in severity of cystic phenotype compared to mutant mice wild-type for Flcn
|
|
• no increase in severity of phenotype compared to mutant mice wild-type for Flcn
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• survival time is about 3 weeks
|
|
• increased respiratory capacity and mitochondrial surface area indicating increased mitochondrial biogenesis
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• occasional tiny cysts
|
|
• occasional tiny cysts
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mitochondria are swollen with rupture of the membrane and distorted cristae
|
|
• rupture of mitochondrial membranes in renal tubular epithelial cells
|
|
• distorted in renal tubular epithelial cells
|
|
• swollen mitochondria in renal tubular epithelial cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• 1,25(OH)2D calcium and creatinine levels are normal
|
|
• in mice fed standard chow
|
|
• in mice are fed a high phosphate diet
|
|
• in mice fed standard chow
• more so when mice are fed a high phosphate diet
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
Nephrocalcinosis in Cldn10tm1.1Dmu/Cldn10tm1.1Dmu Tg(Cdh16-cre)91Igr/0 kidneys
|
• increase in K+ fractional excretion
|
|
• slight decrease in fractional excretion of Ca2+
• however, serum calcium levels are not increased
|
|
• fractional excretion of Mg2+ is only 52% of controls
|
|
• parallels increased urine volume
|
|
• 1.4 fold lower fractional excretion of urea
|
|
• extensive medullary calcium deposits at 10 weeks of age along the outer stripe of the outer medulla and in the inner stripe of the outer medulla at the transition to the inner medulla
|
|
• in freshly isolated tubule thick ascending limbs the permeability sequence for different cations are altered from monovalent to divalent
|
|
• increase in Mg2+ reabsorbtion
|
|
• slight increased
|
|
• moderate
|
|
• 1.4 fold higher serum urea concentration
|
|
• increased 2 fold
|
|
• 28% higher
|
|
• slight increased
|
|
• increase in K+ fractional excretion
|
|
• slight decrease in fractional excretion of Ca2+
• however, serum calcium levels are not increased
|
|
• fractional excretion of Mg2+ is only 52% of controls
|
|
• parallels increased urine volume
|
|
• 1.4 fold lower fractional excretion of urea
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice die between P14 and P17 of renal failure
|
|
• at P7, proliferation of the cyst lining cells in the kidney is increased compared to in wild-type mice
|
|
• mice exhibit a rapid progression of polycystic disease
|
|
• an increased kidney weight to body weight ratio is observed at day 4 and increases rapidly thereafter
|
|
• mice die between P14 and P17 of renal failure
|
|
• the rapid increase in blood urea nitrogen level is associated with the cystic enlargement of the kidneys
|
|
• at two weeks of age
|
|
• at two weeks of age
|
|
• mice exhibit a rapid progression of polycystic disease
|
|
• an increased kidney weight to body weight ratio is observed at day 4 and increases rapidly thereafter
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice die between P14 and P17 of renal failure
|
|
• at P7, proliferation of the cyst lining cells in the kidney is increased compared to in wild-type mice
|
|
• mice exhibit a rapid progression of polycystic disease
|
|
• an increased kidney weight to body weight ratio is observed at day 4 and increases rapidly thereafter
|
|
• mice die between P14 and P17 of renal failure
|
|
• the rapid increase in blood urea nitrogen level is associated with the cystic enlargement of the kidneys
|
|
• at two weeks of age
|
|
• at two weeks of age
|
|
• mice exhibit a rapid progression of polycystic disease
|
|
• an increased kidney weight to body weight ratio is observed at day 4 and increases rapidly thereafter
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| polycystic kidney disease 1 | DOID:0110858 |
OMIM:173900 |
J:135301 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice die at around P60
|
|
• at P14, most DBA-positive collecting duct epithelial cells are devoid of cilia, indicating a cilia biogenesis defect
|
|
• at P14, kidneys exhibit ~14% of BrdU-positive nuclei in DBA-positive cyst-lining cells versus ~2.8% in control kidneys, suggesting a significant increase in cell proliferation
|
|
• mice show rapid kidney cyst formation, with minimal cysts at P7, significant cysts in both the medulla and cortex region at P14, and severely cystic kidneys at P17
• cyst formation is confined to the distal nephron
• at P14, cysts mainly form in the collecting duct; by P28, cysts are detected in the medullary thick ascending limb and the distal convoluted tubule
|
|
• significant cysts in the cortex region at P14
|
|
• significant cysts in the medulla region at P14
|
|
• mice exhibit rapid progression of polycystic kidney disease (PKD) with severely cystic kidneys at P17
• treatment with valproic acid (VPA, a histone deacetylase inhibitor) can partially suppress PKD progression
|
|
• starting at P14, kidney size is obviously enlarged; by P17, kidney size is significantly increased
• mice treated with valproic acid (VPA, a histone deacetylase inhibitor) from P10 to P25 show significantly reduced kidney size relative to vehicle-treated controls
|
|
• at P14, kidney-to-body weight ratio is significantly increased
• mice treated with VPA from P10 to P25 show a significantly reduced kidney-to-body weight ratio relative to vehicle-treated controls
|
|
• at P7, some DBA-positive regions marking the collecting ducts are already dilated
• in dilated regions, cilia are largely absent, whereas cilia are still present in non-dilated DBA-positive regions
|
|
• at P28, but not at P21, kidneys exhibit increased trichrome staining indicating collagen deposition
• mice treated with VPA from P10 to P25 show a significantly reduced collagen deposition relative to vehicle-treated controls
|
|
• at P28, kidney interstitial cells show a dramatic increase in smooth muscle actin expression relative to controls
• VPA treatment from P10 to P25 significantly reduces smooth muscle actin expression in the interstitium
|
|
• mice develop rapidly progressive renal failure
|
|
• BUN level is significantly increased at P14
• mice treated with VPA from P10 to P25 show a significantly reduced BUN level, indicating improved kidney function
|
|
• at P14, most DBA-positive collecting duct epithelial cells are devoid of cilia, indicating a cilia biogenesis defect
|
|
• at P14, kidneys exhibit ~14% of BrdU-positive nuclei in DBA-positive cyst-lining cells versus ~2.8% in control kidneys, suggesting a significant increase in cell proliferation
|
|
• mice show rapid kidney cyst formation, with minimal cysts at P7, significant cysts in both the medulla and cortex region at P14, and severely cystic kidneys at P17
• cyst formation is confined to the distal nephron
• at P14, cysts mainly form in the collecting duct; by P28, cysts are detected in the medullary thick ascending limb and the distal convoluted tubule
|
|
• significant cysts in the cortex region at P14
|
|
• significant cysts in the medulla region at P14
|
|
• mice exhibit rapid progression of polycystic kidney disease (PKD) with severely cystic kidneys at P17
• treatment with valproic acid (VPA, a histone deacetylase inhibitor) can partially suppress PKD progression
|
|
• starting at P14, kidney size is obviously enlarged; by P17, kidney size is significantly increased
• mice treated with valproic acid (VPA, a histone deacetylase inhibitor) from P10 to P25 show significantly reduced kidney size relative to vehicle-treated controls
|
|
• at P14, kidney-to-body weight ratio is significantly increased
• mice treated with VPA from P10 to P25 show a significantly reduced kidney-to-body weight ratio relative to vehicle-treated controls
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• significantly aggravated renal injuries following ischemia/reperfusion injury with increase tubule epithelial cell death and exacerbated inflammation
• following ischemia/reperfusion levels of blood urea nitrogen and serum creatinine are increased compared to similarly treated wild-type controls
• elevated levels of oxidized RNA following ischemia/reperfusion injury compared to similarly treated wild-type controls
|
|
• more severe inflammation after ishcenia/reperfusion injury compared to similarly treated wild-type controls
|
|
• after ischemia/reperfusion injury compared to similarly treated wild-type mice
• baseline creatinine is similar to controls
|
|
• after ischemia/reperfusion injury compared to similarly treated wild-type mice
• baseline BUN is similar to controls
|
|
• significantly aggravated renal injuries following ischemia/reperfusion injury with increase tubule epithelial cell death and exacerbated inflammation
• following ischemia/reperfusion levels of blood urea nitrogen and serum creatinine are increased compared to similarly treated wild-type controls
• elevated levels of oxidized RNA following ischemia/reperfusion injury compared to similarly treated wild-type controls
|
|
• more severe inflammation after ishcenia/reperfusion injury compared to similarly treated wild-type controls
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice exhibit slow cyst growth
|
|
• mice develop renal fibrosis
|
|
• mice exhibit slow cyst growth
|
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 06/12/2024 MGI 6.13 |
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