Mouse Genome Informatics
ht1
    Vhltm1.1Lss/Vhl+
involves: A/J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
liver/biliary system
• 66% showed hepatic vascular lesions on a A/J genetic background

Mouse Models of Human Disease
OMIM IDRef(s)
Von Hippel-Lindau Syndrome; VHL 193300 J:85513


Mouse Genome Informatics
ht2
    Vhltm1.1Lss/Vhl+
involves: BALB/c
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• 88% showed hepatic hemangiomas by 18 months of age, on a BALB/c genetic background

Mouse Models of Human Disease
OMIM IDRef(s)
Von Hippel-Lindau Syndrome; VHL 193300 J:85513


Mouse Genome Informatics
ht3
    Vhltm1Lss/Vhltm1.1Lss
involves: 129X1/SvJ * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• observed in 18% of mice between 4 and 12 months of age, putatively due to sporadic LOH
• smaller than those observed in Vhlhtm1Lss/ Vhlhtm1.1Lss;Tg(ACTB-cre)1Tes mice

reproductive system
• 2-fold reduction in sperm count relative to wild-type (J:85513)

Mouse Models of Human Disease
OMIM IDRef(s)
Von Hippel-Lindau Syndrome; VHL 193300 J:85513


Mouse Genome Informatics
cn4
    Vhltm1Lss/Vhltm1.1Lss
Tg(CAG-cre/Esr1*)1Lbe/0

involves: 129S1/Sv * 129X1/SvJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• all embryos of pregnant females injected with 2 mg of tamoxifen at E10.5 to inactive Vhlh during mid-gestational stage, die between E14.5 and E15.5

growth/size
• embryos of pregnant females injected with tamoxifen at E10.5 are smaller than controls

cardiovascular system
• treatment of pregnant females at E10.5 with tamoxifen results in abnormal vasculature and dilated blood vessels in the body of E14.7 embryos
• dilated vessels are frequently seen after tamoxifen treatment
• treatment of pregnant females at E10.5 with tamoxifen results in impaired blood circulation in the yolk sac of E14.7 embryos
• treatment of pregnant females at E10.5 with tamoxifen results in hemorrhage in the dorsolateral region of embryos at E14.5

cellular
• at 24 hrs after bilateral renal ischemia-reperfusion injury (IRI), tamoxifen-treated mice exhibit significantly fewer TUNEL+ cells in the proximal tubules relative to tamoxifen-treated control mice
• treatment of pregnant females at E10.5 with tamoxifen results in extensive embryo necrosis

embryogenesis
• treatment of pregnant females at E10.5 with tamoxifen results in impaired blood circulation in the yolk sac of E14.7 embryos
• embryos of pregnant females injected with tamoxifen at E10.5 are smaller than controls
• when pregnant females are injected with tamoxifen at E10.5, frequently observe dilated blood vessels and spongiotriophoblast cells in the labyrinthine layer
• dilated vessels are frequently seen after tamoxifen treatment
• thickness of the labyrinthine layer is reduced when pregnant females are injected with tamoxifen at E10.5

liver/biliary system
• treatment of pregnant females at E10.5 with tamoxifen results in focal necrosis in the liver or E14.5 embryos

integument
• seen in embryos of pregnant females injected with tamoxifen at E10.5

homeostasis/metabolism
• at 24 hrs after bilateral renal ischemia-reperfusion injury (IRI), tamoxifen-treated mice exhibit significantly lower serum creatinine levels than tamoxifen-treated control mice (0.24 +/- 0.04 mg/dl versus 0.72 +/- 0.16 mg/dL, respectively)
• at 24 hrs after bilateral renal IRI, tamoxifen-treated mice exhibit significantly lower serum BUN levels than tamoxifen-treated control mice (52.12 +/- 6.61 mg/dl versus 138.10 +/- 13.03 mg/dL, respectively)
• at 24 hrs after bilateral renal IRI, tamoxifen-treated mice (0.36mg/g body weight injected i.p. one wk prior to IRI) exhibit better preservation of renal function and significantly lower tubular injury scores than tamoxifen-treated control mice (2.40 +/- 0.08 and 0.90 +/- 0.12, respectively), consistent with reduced proximal tubular injury, near absence of TUNEL+ cells, and milder tubular epithelial degeneration

renal/urinary system
• at 24 hrs after bilateral renal ischemia-reperfusion injury (IRI), tamoxifen-treated mice exhibit significantly fewer TUNEL+ cells in the proximal tubules relative to tamoxifen-treated control mice
• at 24 hrs after bilateral renal IRI, tamoxifen-treated mice (0.36mg/g body weight injected i.p. one wk prior to IRI) exhibit better preservation of renal function and significantly lower tubular injury scores than tamoxifen-treated control mice (2.40 +/- 0.08 and 0.90 +/- 0.12, respectively), consistent with reduced proximal tubular injury, near absence of TUNEL+ cells, and milder tubular epithelial degeneration


Mouse Genome Informatics
cn5
    Vhltm1Lss/Vhltm1.1Lss
Tg(ACTB-cre)1Tes/0

involves: 129X1/SvJ * C3H * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• mice began to die after 3 months of age
• 50% mortalitiy exhibited by 7 months of age
• 90% mortalitiy by 1 year of age

tumorigenesis
• all mice displayed grossly visible hemangiomas by 1 year of age

cardiovascular system
• frequent angiectasis in the liver and with lesser penetrance in the kidneys
• increased vasculature of the pancreas
• no vascular lesions observed in the brain, ovary, or adrenal glands
• limited new blood vessel formation in the liver
• angiogenesis observed the cardiac muscle of 8 of 10 mice examined

endocrine/exocrine glands
• enlarged blood vessels in the connective tissue surrounding the tubules (J:85513)
• tubule atrophy and collapse (J:85513)
(J:85513)

liver/biliary system
• livers were irregularly shaped and had vascular lesions containing large, thin-walled vessels filled with blood

reproductive system
• enlarged blood vessels in the connective tissue surrounding the tubules (J:85513)
• tubule atrophy and collapse (J:85513)
(J:85513)
• abnormal sperm maturation with multinucleated giant cells (J:85513)
• 30-fold reduction in sperm count relative to wild-type (J:85513)
(J:85513)

Mouse Models of Human Disease
OMIM IDRef(s)
Von Hippel-Lindau Syndrome; VHL 193300 J:85513