Phenotypes associated with this allele

• Allele Symbol: Srgap1^{tm1a(KOMP)Wtsi}
• Allele Name: targeted mutation 1a, Wellcome Trust Sanger Institute
• Allele ID: MGI:5432204
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Srgap1^tm1a(KOMP)Wtsi/Srgap1^tm1a(KOMP)Wtsi Six2^tm1(tTA,tetO-EGFP/cre)Amc/Six2^+	involves: 129 * C57BL/6J * C57BL/6N	MGI:7442509
cn2	Srgap1^tm1a(KOMP)Wtsi/Srgap1^tm1a(KOMP)Wtsi Tg(NPHS2-cre)295Lbh/0	involves: C57BL/6 * C57BL/6N * SJL	MGI:7442514

Genotype
MGI:7442509

cn1

• Allelic Composition: Srgap1^{tm1a(KOMP)Wtsi}/Srgap1^{tm1a(KOMP)Wtsi}; Six2^{tm1(tTA,tetO-EGFP/cre)Amc}/Six2⁺
• Genetic Background: involves: 129 * C57BL/6J * C57BL/6N
• Cell Lines: EPD0153_3_C10

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

renal/urinary system

increased mesangial cell number ( J:333727 )

• increased mesangial cell proliferation at 12 weeks of age

detached podocyte ( J:333727 )

• podocyte detachment at 12 weeks of age

albuminuria ( J:333727 )

• progressive albuminuria, starting at 6 weeks after birth

• however, no increase in proteinuria is detected at birth

podocyte foot process effacement ( J:333727 )

• TEM analysis showed pronounced widening and misconfiguration (effacement) of podocyte foot processes at 8 and 12 weeks of age

• 3D SIM microscopy showed reduced filtration slit density (FSD), indicating aberrant foot process architecture at 8 weeks of age

• SEM revealed marked simplification, reduced branching, and misconfiguration of podocyte foot processes

absent podocyte slit diaphragm ( J:333727 )

• marked rarefaction and loss of slit diaphragms at 12 weeks of age

decreased podocyte number ( J:333727 )

• progressive podocyte loss

expanded mesangial matrix ( J:333727 )

• mesangial sclerosis at 12 weeks of age

glomerulosclerosis ( J:333727 )

• mice develop a nephrotic syndrome with a late-onset focal segmental glomerulosclerosis (FSGS)-like phenotype in adulthood

• a significantly increased glomerulosclerosis score is noted at 8 and 12 weeks of age

dilated renal tubule ( J:333727 )

• tubular dilation at 12 weeks of age

renal cast ( J:333727 )

• formation of proteinaceous casts at 12 weeks of age

abnormal glomerular filtration barrier function ( J:333727 )

• progressive loss of filtration-barrier function, starting at 6 weeks after birth

cellular

increased mesangial cell number ( J:333727 )

• increased mesangial cell proliferation at 12 weeks of age

detached podocyte ( J:333727 )

• podocyte detachment at 12 weeks of age

homeostasis/metabolism

albuminuria ( J:333727 )

• progressive albuminuria, starting at 6 weeks after birth

• however, no increase in proteinuria is detected at birth

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
focal segmental glomerulosclerosis		DOID:1312	OMIM:PS603278	J:333727

Genotype
MGI:7442514

cn2

• Allelic Composition: Srgap1^{tm1a(KOMP)Wtsi}/Srgap1^{tm1a(KOMP)Wtsi}; Tg(NPHS2-cre)295Lbh/0
• Genetic Background: involves: C57BL/6 * C57BL/6N * SJL
• Cell Lines: EPD0153_3_C10

renal/urinary system

renal/urinary system phenotype ( J:333727 )

N • unchallenged mice exhibit no overt renal phenotype up to 24 weeks of age, as assessed by measurement of albuminuria and histology

increased mesangial cell number ( J:333727 )

• increased mesangial cell proliferation in response to doxorubicin-induced podocyte injury

albuminuria ( J:333727 )

• increased urinary albumin-creatinine ratio in response to doxorubicin-induced podocyte injury

glomerulosclerosis ( J:333727 )

• increased segmental glomerulosclerosis in response to doxorubicin-induced podocyte injury

homeostasis/metabolism

albuminuria ( J:333727 )

• increased urinary albumin-creatinine ratio in response to doxorubicin-induced podocyte injury

increased susceptibility to injury ( J:333727 )

• following injection of adriamycin (doxorubicin) at 6 weeks of age to induce podocyte injury, 14-week-old mice exhibit histologic lesions and a significantly higher urinary albumin-creatinine ratio and glomerulosclerosis score than similarly treated control mice

cellular

increased mesangial cell number ( J:333727 )

• increased mesangial cell proliferation in response to doxorubicin-induced podocyte injury