Phenotypes associated with this allele

• Allele Symbol: Vhl^tm1Lss
• Allele Name: targeted mutation 1, Laura S Schmidt
• Allele ID: MGI:2677574
• Summary: 7 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
ht1	Vhl^tm1Lss/Vhl^tm1.1Lss	involves: 129X1/SvJ * C57BL/6	MGI:2677761
cn2	Vhl^tm1Lss/Vhl^tm1Lss Tg(Pdx1-cre)89.1Dam/0	either: (involves: 129X1/SvJ * A/J * C57BL/6 * CBA) or (involves: 129X1/SvJ * BALB/c * C57BL/6 * CBA)	MGI:3844063
cn3	Vhl^tm1Lss/Vhl^tm1Lss Tg(Gcg-cre)1Slib/0	either: (involves: 129X1/SvJ * A/J) or (involves: 129X1/SvJ * C57BL/6)	MGI:3844061
cn4	Vhl^tm1Lss/Vhl^tm1Lss Tg(Ins2-cre)25Mgn/0	either: (involves: 129X1/SvJ * C57BL/6 * DBA) or (involves: 129X1/SvJ * A/J * C57BL/6 * DBA)	MGI:3844062
cn5	Vhl^tm1Lss/Vhl^tm1.1Lss Tg(CAG-cre/Esr1*)1Lbe/0	involves: 129S1/Sv * 129X1/SvJ	MGI:3653510
cn6	Vhl^tm1Lss/Vhl^tm1.1Lss Tg(ACTB-cre)1Tes/0	involves: 129X1/SvJ * C3H * C57BL/6	MGI:2677759
cn7	Vhl^tm1Lss/Vhl^tm1Lss Tg(Pdx1-cre)89.1Dam/0	involves: 129X1/SvJ * C57BL/6 * CBA	MGI:3844065

Genotype
MGI:2677761

ht1

• Allelic Composition: Vhl^tm1Lss/Vhl^tm1.1Lss
• Genetic Background: involves: 129X1/SvJ * C57BL/6

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

neoplasm

increased hepatic hemangioma incidence ( J:85513 )

• 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

reproductive system

oligozoospermia ( J:85513 )

♂ • 2-fold reduction in sperm count relative to wild-type

liver/biliary system

increased hepatic hemangioma incidence ( J:85513 )

• 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

cellular

oligozoospermia ( J:85513 )

♂ • 2-fold reduction in sperm count relative to wild-type

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
von Hippel-Lindau disease		DOID:14175	OMIM:193300	J:85513

Genotype
MGI:3844063

cn2

• Allelic Composition: Vhl^tm1Lss/Vhl^tm1Lss; Tg(Pdx1-cre)89.1Dam/0
• Genetic Background: either: (involves: 129X1/SvJ * A/J * C57BL/6 * CBA) or (involves: 129X1/SvJ * BALB/c * C57BL/6 * CBA)

mortality/aging

postnatal lethality, incomplete penetrance ( J:148174 )

• numbers of mutant offspring identified at weaning (15.3%) are significantly lower than expected Mendelian numbers (25%)

• expected numbers of double mutant offspring are present embryonically and at birth, but many die by P5

Genotype
MGI:3844061

cn3

• Allelic Composition: Vhl^tm1Lss/Vhl^tm1Lss; Tg(Gcg-cre)1Slib/0
• Genetic Background: either: (involves: 129X1/SvJ * A/J) or (involves: 129X1/SvJ * C57BL/6)

mortality/aging

mortality/aging ( J:148174 )

N • expected Mendelian numbers of offspring are detected at weaning; no obvious behavioral or physiological abnormalities are detected

endocrine/exocrine glands

endocrine/exocrine gland phenotype ( J:148174 )

N • pancreases appears histologically normal compared to controls from 10-23 months

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
von Hippel-Lindau disease		DOID:14175	OMIM:193300	J:148174

Genotype
MGI:3844062

cn4

• Allelic Composition: Vhl^tm1Lss/Vhl^tm1Lss; Tg(Ins2-cre)25Mgn/0
• Genetic Background: either: (involves: 129X1/SvJ * C57BL/6 * DBA) or (involves: 129X1/SvJ * A/J * C57BL/6 * DBA)

mortality/aging

mortality/aging ( J:148174 )

N • expected Mendelian numbers of offspring are detected at weaning; no obvious behavioral or physiological abnormalities are detected

endocrine/exocrine glands

endocrine/exocrine gland phenotype ( J:148174 )

N • pancreases appears histologically normal compared to controls from 10-23 months

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
von Hippel-Lindau disease		DOID:14175	OMIM:193300	J:148174

Genotype
MGI:3653510

cn5

• Allelic Composition: Vhl^tm1Lss/Vhl^tm1.1Lss; Tg(CAG-cre/Esr1*)1Lbe/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

mortality/aging

lethality throughout fetal growth and development, complete penetrance ( J:110518 )

• 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/body

decreased embryo size ( J:110518 )

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

cardiovascular system

abnormal blood vessel morphology ( J:110518 )

• treatment of pregnant females at E10.5 with tamoxifen results in abnormal vasculature and dilated blood vessels in the body of E14.7 embryos

abnormal placental labyrinth vasculature morphology ( J:110518 )

• dilated vessels are frequently seen after tamoxifen treatment

abnormal vitelline vasculature morphology ( J:110518 )

• treatment of pregnant females at E10.5 with tamoxifen results in impaired blood circulation in the yolk sac of E14.7 embryos

hemorrhage ( J:110518 )

• treatment of pregnant females at E10.5 with tamoxifen results in hemorrhage in the dorsolateral region of embryos at E14.5

cellular

decreased renal tubule apoptosis ( J:155367 )

• 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

embryo

abnormal vitelline vasculature morphology ( J:110518 )

• treatment of pregnant females at E10.5 with tamoxifen results in impaired blood circulation in the yolk sac of E14.7 embryos

decreased embryo size ( J:110518 )

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

embryo tissue necrosis ( J:110518 )

• treatment of pregnant females at E10.5 with tamoxifen results in extensive embryo necrosis

abnormal placenta labyrinth morphology ( J:110518 )

• when pregnant females are injected with tamoxifen at E10.5, frequently observe dilated blood vessels and spongiotriophoblast cells in the labyrinthine layer

abnormal placental labyrinth vasculature morphology ( J:110518 )

• dilated vessels are frequently seen after tamoxifen treatment

thin placenta labyrinth ( J:110518 )

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

liver/biliary system

focal hepatic necrosis ( J:110518 )

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

integument

pallor ( J:110518 )

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

homeostasis/metabolism

decreased circulating creatinine level ( J:155367 )

• 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)

decreased blood urea nitrogen level ( J:155367 )

• 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)

decreased susceptibility to kidney reperfusion injury ( J:155367 )

• 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

decreased renal tubule apoptosis ( J:155367 )

• 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

decreased susceptibility to kidney reperfusion injury ( J:155367 )

• 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

Genotype
MGI:2677759

cn6

• Allelic Composition: Vhl^tm1Lss/Vhl^tm1.1Lss; Tg(ACTB-cre)1Tes/0
• Genetic Background: involves: 129X1/SvJ * C3H * C57BL/6

mortality/aging

premature death ( J:85513 )

• mice began to die after 3 months of age

• 50% mortalitiy exhibited by 7 months of age

• 90% mortalitiy by 1 year of age

reproductive system

oligozoospermia ( J:85513 )

♂ • 30-fold reduction in sperm count relative to wild-type

multinucleated giant male germ cells ( J:85513 )

♂ • abnormal sperm maturation with multinucleated giant cells

decreased Sertoli cell number ( J:85513 )

♂

seminiferous tubule degeneration ( J:85513 )

♂ • enlarged blood vessels in the connective tissue surrounding the tubules

♂ • tubule atrophy and collapse

small testis ( J:85513 )

♂

male infertility ( J:85513 )

♂

neoplasm

increased hepatic hemangioma incidence ( J:85513 )

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

cardiovascular system

abnormal blood vessel morphology ( J:85513 )

• 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

abnormal angiogenesis ( J:85513 )

• limited new blood vessel formation in the liver

• angiogenesis observed the cardiac muscle of 8 of 10 mice examined

liver/biliary system

abnormal liver morphology ( J:85513 )

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

increased hepatic hemangioma incidence ( J:85513 )

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

endocrine/exocrine glands

decreased Sertoli cell number ( J:85513 )

♂

seminiferous tubule degeneration ( J:85513 )

♂ • enlarged blood vessels in the connective tissue surrounding the tubules

♂ • tubule atrophy and collapse

small testis ( J:85513 )

♂

cellular

oligozoospermia ( J:85513 )

♂ • 30-fold reduction in sperm count relative to wild-type

multinucleated giant male germ cells ( J:85513 )

♂ • abnormal sperm maturation with multinucleated giant cells

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
von Hippel-Lindau disease		DOID:14175	OMIM:193300	J:85513

Genotype
MGI:3844065

cn7

• Allelic Composition: Vhl^tm1Lss/Vhl^tm1Lss; Tg(Pdx1-cre)89.1Dam/0
• Genetic Background: involves: 129X1/SvJ * C57BL/6 * CBA

Vhl^tm1Lss/Vhl^tm1Lss Tg(Pdx1-cre)89.1Dam/0 mice develop microcystic adenomas in the pancreas

mortality/aging

postnatal lethality, incomplete penetrance ( J:148174 )

• numbers of mutant offspring identified at weaning (3.7%) are significantly lower than expected Mendelian numbers (25%)

• expected numbers of double mutant offspring are present embryonically and at birth, but many die by P5

neoplasm

increased pancreas adenoma incidence ( J:148174 )

• at 6-7 months of age, pancreases are indistinguishable from controls; at 16-18 months of age, microcystic adenomas (MCA) are identified; extensive vasculature network is observed in MCA, similar to what is seen in human VHL patients

endocrine/exocrine glands

abnormal exocrine pancreas morphology ( J:148174 )

• at 16-18 months of age, significant loss of exocrine pancreas and replacement with fat deposition is observed

abnormal pancreatic islet morphology ( J:148174 )

• at 16-18 months of age, some islets appear small and abnormally shaped without many exocrine acinar cells surrounding them

increased pancreas adenoma incidence ( J:148174 )

• at 6-7 months of age, pancreases are indistinguishable from controls; at 16-18 months of age, microcystic adenomas (MCA) are identified; extensive vasculature network is observed in MCA, similar to what is seen in human VHL patients

pancreas cyst ( J:148174 )

• at 6-7 months of age, pancreases are indistinguishable from controls; at 16-18 months of age, cysts are identified

digestive/alimentary system

abnormal exocrine pancreas morphology ( J:148174 )

• at 16-18 months of age, significant loss of exocrine pancreas and replacement with fat deposition is observed

growth/size/body

pancreas cyst ( J:148174 )

• at 6-7 months of age, pancreases are indistinguishable from controls; at 16-18 months of age, cysts are identified

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
von Hippel-Lindau disease		DOID:14175	OMIM:193300	J:148174