Phenotypes associated with this allele

• Allele Symbol: Hs3st3a1^em1Jiliu
• Allele Name: endonuclease-mediated mutation 1, Jian Liu
• Allele ID: MGI:8460917
• Summary: 1 genotype

Jump to	Allelic Composition	Genetic Background	Genotype ID
cx1	Hs3st3b1^tm1(KOMP)Vlcg/Hs3st3b1^tm1(KOMP)Vlcg Hs3st3a1^em1Jiliu/Hs3st3a1^em1Jiliu	C57BL/6NTac-Hs3st3a1^em1Jiliu Hs3st3b1^tm1(KOMP)Vlcg	MGI:8235828

Genotype
MGI:8235828

cx1

• Allelic Composition: Hs3st3b1^{tm1(KOMP)Vlcg}/Hs3st3b1^{tm1(KOMP)Vlcg}; Hs3st3a1^em1Jiliu/Hs3st3a1^em1Jiliu
• Genetic Background: C57BL/6NTac-Hs3st3a1^em1Jiliu Hs3st3b1^{tm1(KOMP)Vlcg}

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

renal/urinary system

decreased urine protein level ( J:360826 )

♀ • adult females, but not males, show a significant decrease in urinary vitamin D binding protein (VDBP) levels relative to wild-type controls

♀ • however, both sexes show normal urinary levels of albumin, creatinine, nephrin, and alpha-1-microglobulin relative to wild-type controls, with no differences in the albumin/creatinine ratio, suggesting normal glomerular function

fused podocyte foot processes ( J:360826 )

• glomeruli can have fused podocyte foot processes

podocyte foot process effacement ( J:360826 )

• glomeruli can have fused or unevenly spaced podocyte foot processes

• TEM analysis shows podocyte foot process effacement, suggesting that 3-O-sulfation is important for podocyte adhesion to the GBM

abnormal renal glomerulus basement membrane morphology ( J:360826 )

• TEM analysis shows an irregular and thickened GBM; glomeruli can have normal looking GBM or an uneven thickening of GBM

increased renal glomerulus basement membrane thickness ( J:360826 )

abnormal renal glomerulus morphology ( J:360826 )

• adult kidneys show a significant reduction in glomerular size; cortical glomeruli are ~20% smaller in males and ~10% smaller in females

• glomeruli exhibit decreased heparan sulfate proteoglycans (HSPG) stubs and LACE binding to GBM: 3G10 staining of total HSPG core proteins and binding of FGF10-FGFR2b complex to endogenous HS indicates that loss of the highly 3-O-sulfated domain modifies glomerular HS and may affect growth factor binding

• male, but not female, glomeruli show increased phospho-ERK1/2 (pERK) staining, suggesting increased growth factor signaling

• however, kidneys show no transcriptional changes in the expression of glomerular basement membrane (GBM) components

renal glomerular protein deposits ( J:360826 )

• glomeruli exhibit an increase in collagen type IV (COLIV) staining

• however, isolated glomeruli show no transcriptional changes in the expression of GBM components

decreased kidney weight ( J:360826 )

• adult kidney weight is significantly lower than in wild-type controls, showing a 14% reduction in males and an 11% reduction in females

homeostasis/metabolism

increased blood urea nitrogen level ( J:360826 )

• adult mice show a modest increase in BUN levels in both sexes

decreased urine protein level ( J:360826 )

♀ • adult females, but not males, show a significant decrease in urinary vitamin D binding protein (VDBP) levels relative to wild-type controls

♀ • however, both sexes show normal urinary levels of albumin, creatinine, nephrin, and alpha-1-microglobulin relative to wild-type controls, with no differences in the albumin/creatinine ratio, suggesting normal glomerular function

abnormal metabolism ( J:360826 )

• LC-MS/MS analysis of kidney heparan sulfate (HS) shows loss of detection of the most highly sulfated tetrasaccharide, deltaUA-GlcNS6S-IdoA2S-GlcNS3S6S and a decrease in deltaUA-GlcNS6S-GlcA-GlcNS3S6S, containing the 3-O-sulfated antithrombin binding site

• in addition, both deltaUA-GlcNS-IdoA2S-GlcNS3S and deltaUA2S-GlcNS-IdoA2S-GlcNS3S are decreased, indicating an overall decrease in total 3-O-sulfation in the kidney HS

• however, no differences are observed in the composition of seven disaccharides relative to wild-type controls