• 66% showed hepatic vascular lesions on a A/J genetic background

• 88% showed hepatic hemangiomas by 18 months of age, on a BALB/c genetic background

• observed in 18% of mice between 4 and 12 months of age, putatively due to sporadic LOH

• smaller than those observed in Vhlh^tm1Lss/ Vhlh^tm1.1Lss;Tg(ACTB-cre)1Tes mice

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

• 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

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

• 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

• 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

• 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

• thickness of the labyrinthine layer is reduced when pregnant females are injected with tamoxifen at E10.5

• 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

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

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

• 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

• 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

• mice began to die after 3 months of age

• 50% mortalitiy exhibited by 7 months of age

• 90% mortalitiy by 1 year of age

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

• 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

• enlarged blood vessels in the connective tissue surrounding the tubules (J:85513)

• tubule atrophy and collapse (J:85513)

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

• enlarged blood vessels in the connective tissue surrounding the tubules (J:85513)

• tubule atrophy and collapse (J:85513)

• abnormal sperm maturation with multinucleated giant cells (J:85513)

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