Phenotypes associated with this allele

• Allele Symbol: Wt1^tm1Mlh
• Allele Name: targeted mutation 1, Martin L Hooper
• Allele ID: MGI:3794650
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Wt1^tm1Mlh/Wt1^tm1Mlh	involves: 129P2/OlaHsd * C57BL/6	MGI:3803670
ht2	Wt1^tm1Mlh/Wt1^+	129P2/OlaHsd-Wt1^tm1Mlh	MGI:3803666
ht3	Wt1^tm1Mlh/Wt1^+	involves: 129P2/OlaHsd * C57BL/6	MGI:3803665
ht4	Wt1^tm1Mlh/Wt1^+	involves: 129P2/OlaHsd * C57BL/6 * MF1	MGI:3803667

Genotype
MGI:3803670

hm1

• Allelic Composition: Wt1^tm1Mlh/Wt1^tm1Mlh
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

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

mortality/aging

lethality throughout fetal growth and development, complete penetrance ( J:135449 )

• homozygotes are embryonic lethal

• 17% of embryos die by E12.5 and 71% of embryos die by E13.5

embryonic lethality during organogenesis, incomplete penetrance ( J:135449 )

• 17% of embryos die by E12.5

growth/size/body

decreased embryo size ( J:135449 )

• embryo size is reduced at E12.5 and E13.5 compared to age-matched control embryos

endocrine/exocrine glands

abnormal adrenal gland development ( J:135449 )

• adrenal primordia in E13.5 embryos are significantly smaller

agonadal ( J:135449 )

• gonads are absent in all E13.5 embryos

absent ovary ( J:135449 )

♀

absent testes ( J:135449 )

♂

embryo

decreased embryo size ( J:135449 )

• embryo size is reduced at E12.5 and E13.5 compared to age-matched control embryos

reproductive system

agonadal ( J:135449 )

• gonads are absent in all E13.5 embryos

absent ovary ( J:135449 )

♀

absent testes ( J:135449 )

♂

renal/urinary system

abnormal kidney development ( J:135449 )

• E13.5 embryos fail to develop a metanephros

absent metanephros ( J:135449 )

cardiovascular system

myocardium hypoplasia ( J:135449 )

abnormal heart development ( J:135449 )

• cardiac dysplasia is noted in all embryos at E13.5

• both ventricles have poorly developing compact and trabecular myocardium in the free walls

• atrial cavaties are dilated with thickened epicardium

• other cardiac abnormalities noted in E13.5 embryos are hypoplastic myocardium, heart shape abnormalities with rounded apex, and improper epicardium and mesocardial attachment

abnormal heart apex morphology ( J:135449 )

• rounded heart apex

abnormal heart shape ( J:135449 )

hemopericardium ( J:135449 )

• pericardial hemorrhaging in about half the embryos

liver/biliary system

abnormal liver development ( J:135449 )

• the livers of E12.5 and E13.5 embryos are hypoplastic and deficient in lobation

liver hypoplasia ( J:135449 )

muscle

myocardium hypoplasia ( J:135449 )

abnormal diaphragm development ( J:135449 )

• diaphragms are incompletely formed in all embryos at E12.5 with an increase in the dorsolateral gap

• E13.5 embyros have large openings between the pleural and peritoneal spaces

homeostasis/metabolism

hemopericardium ( J:135449 )

• pericardial hemorrhaging in about half the embryos

Genotype
MGI:3803666

ht2

• Allelic Composition: Wt1^tm1Mlh/Wt1⁺
• Genetic Background: 129P2/OlaHsd-Wt1^tm1Mlh

renal/urinary system

abnormal mesangial cell morphology ( J:135449 )

• mesangial cells show increased nuclear size and a prominent nucleolus

increased mesangial cell number ( J:135449 )

• mesangial hypercellularity

kidney cortex cyst ( J:135449 )

• microcysts form in the tubules along with protein casts

• cysts are lined by hypertrophic tubular epithelial cells

increased urine protein level ( J:135449 )

• proteinuria is first detected at 54 days of age and occurs in all mice by 18 months of age

• proteinuria occurs after the onset of glomerulosclerosis

glomerulonephritis ( J:135449 )

• inflammatory infiltrates surround damaged blood vessels in the kidney

juxtaglomerular cell hyperplasia ( J:135449 )

• juxtaglomerular hyperplasia is evident in diseased kidneys

podocyte hypertrophy ( J:135449 )

expanded mesangial matrix ( J:135449 )

• increased mesangial matrix leading to obliteration of the glomerular capillary bed

glomerulosclerosis ( J:135449 )

• glomerulosclerosis occurs in about 20-25% of mice by 6 months of age

• onset of glomerulosclerosis occurs earlier than heterozygote mice on a mixed or outbred background

• glomerulosclerosis incidence and severity increases with age

• the disease progresses from a focal and segmental sclerosis to a more diffuse and global pattern

• glomerular tuft collapse and hypertensive nephropathy also occur in the disease kidney

renal cast ( J:135449 )

• protein casts

homeostasis/metabolism

increased urine protein level ( J:135449 )

• proteinuria is first detected at 54 days of age and occurs in all mice by 18 months of age

• proteinuria occurs after the onset of glomerulosclerosis

immune system

glomerulonephritis ( J:135449 )

• inflammatory infiltrates surround damaged blood vessels in the kidney

growth/size/body

kidney cortex cyst ( J:135449 )

• microcysts form in the tubules along with protein casts

• cysts are lined by hypertrophic tubular epithelial cells

cellular

abnormal mesangial cell morphology ( J:135449 )

• mesangial cells show increased nuclear size and a prominent nucleolus

increased mesangial cell number ( J:135449 )

• mesangial hypercellularity

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Denys-Drash syndrome		DOID:3764	OMIM:194080	J:135449

Genotype
MGI:3803665

ht3

• Allelic Composition: Wt1^tm1Mlh/Wt1⁺
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

renal/urinary system

abnormal mesangial cell morphology ( J:135449 )

• mesangial cells show increased nuclear size and a prominent nucleolus

increased mesangial cell number ( J:135449 )

• mesangial hypercellularity

kidney cortex cyst ( J:135449 )

• microcysts form in the tubules along with protein casts

• cysts are lined by hypertrophic tubular epithelial cells

increased urine protein level ( J:135449 )

• proteinuria is detectable in some mice

glomerulonephritis ( J:135449 )

• inflammatory infiltrates surround damaged blood vessels in the kidney

juxtaglomerular cell hyperplasia ( J:135449 )

• juxtaglomerular hyperplasia is evident in diseased kidneys

podocyte hypertrophy ( J:135449 )

expanded mesangial matrix ( J:135449 )

• increased mesangial matrix leading to obliteration of the glomerular capillary bed

glomerulosclerosis ( J:135449 )

• glomerulosclerosis occurs in about half of females and a quarter of males by 15 months of age

• glomerulosclerosis incidence and severity increases with age

• the disease progresses from a focal and segmental sclerosis to a more diffuse and global pattern

• glomerular tuft collapse and hypertensive nephropathy also occur in the diseased kidney

renal cast ( J:135449 )

• protein casts

homeostasis/metabolism

increased urine protein level ( J:135449 )

• proteinuria is detectable in some mice

immune system

glomerulonephritis ( J:135449 )

• inflammatory infiltrates surround damaged blood vessels in the kidney

growth/size/body

kidney cortex cyst ( J:135449 )

• microcysts form in the tubules along with protein casts

• cysts are lined by hypertrophic tubular epithelial cells

cellular

abnormal mesangial cell morphology ( J:135449 )

• mesangial cells show increased nuclear size and a prominent nucleolus

increased mesangial cell number ( J:135449 )

• mesangial hypercellularity

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Denys-Drash syndrome		DOID:3764	OMIM:194080	J:135449

Genotype
MGI:3803667

ht4

• Allelic Composition: Wt1^tm1Mlh/Wt1⁺
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * MF1

renal/urinary system

abnormal mesangial cell morphology ( J:135449 )

• mesangial cells show increased nuclear size and a prominent nucleolus

increased mesangial cell number ( J:135449 )

• mesangial hypercellularity

kidney cortex cyst ( J:135449 )

• microcysts form in the tubules along with protein casts

• cysts are lined by hypertrophic tubular epithelial cells

increased urine protein level ( J:135449 )

• proteinuria is detectable in some mice

glomerulonephritis ( J:135449 )

• inflammatory infiltrates surround damaged blood vessels in the kidney

juxtaglomerular cell hyperplasia ( J:135449 )

• juxtaglomerular hyperplasia is evident in diseased kidneys

podocyte hypertrophy ( J:135449 )

expanded mesangial matrix ( J:135449 )

• increased mesangial matrix leading to obliteration of the glomerular capillary bed

glomerulosclerosis ( J:135449 )

• glomerulosclerosis occurs in about half of of males by 15 months of age

• glomerulosclerosis incidence and severity increases with age

• the disease progresses from a focal and segmental sclerosis to a more diffuse and global pattern

• glomerular tuft collapse and hypertensive nephropathy also occur in the disease kidney

renal cast ( J:135449 )

• protein casts

homeostasis/metabolism

increased urine protein level ( J:135449 )

• proteinuria is detectable in some mice

immune system

glomerulonephritis ( J:135449 )

• inflammatory infiltrates surround damaged blood vessels in the kidney

cellular

abnormal mesangial cell morphology ( J:135449 )

• mesangial cells show increased nuclear size and a prominent nucleolus

increased mesangial cell number ( J:135449 )

• mesangial hypercellularity

growth/size/body

kidney cortex cyst ( J:135449 )

• microcysts form in the tubules along with protein casts

• cysts are lined by hypertrophic tubular epithelial cells

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Denys-Drash syndrome		DOID:3764	OMIM:194080	J:135449