Phenotype Image Detail

Image

Caption

Immunofluorescence analysis of kidneys from 3 month old wild-type (Cd151^+/+, left column), mildly affected, and severely affected Cd151^tm1Nki/Cd151^tm1Nki (Cd151^-/-, second and third column), and 6 week old Itga3^tm1Son/Itga3⁺ Tg(NPHS2-cre)295Lbh/0 (2.5P-Cre; Itga3^+/fl) and Itga3^tm1Son/Itga3^tm1Son Tg(NPHS2-cre)295Lbh/0 (2.5P-Cre; Itga3^fl/fl, colums four and five). The respective proteins are shown in green and red, yielding yellow upon colocalization. Nuclei are counterstained with TOPRO (blue). A-C: Up-regulation of tenascin-C in the mildly affected, and of fibulin-2 in the severely affected, Cd151^tm1Nki/Cd151^tm1Nki glomeruli. D and E: Itga3^tm1Son/Itga3⁺ Tg(NPHS2-cre)295Lbh/0 glomeruli show little presence of tenascin-C, whereas both tenascin-C and fibulin-2 are present in glomeruli of Itga3^tm1Son/Itga3^tm1Son Tg(NPHS2-cre)295Lbh/0 mice. F-I: Integrin alpha3 and alpha6 are localized in glomeruli and tubules, respectively, in both wild-type and mildly affected Cd151^tm1Nki/Cd151^tm1Nki kidneys, as well as in the kidneys of Itga3^tm1Son/Itga3⁺ Tg(NPHS2-cre)295Lbh/0 mice. J: Hardly any alpha3 is present in the glomeruli of Itga3^tm1Son/Itga3^tm1Son Tg(NPHS2-cre)295Lbh/0 mice, whereas alpha6 is normally distributed in the tubules. K and N: Staining of nidogen shows regular GBMs in both wild-type and Itga3^tm1Son/Itga3⁺ Tg(NPHS2-cre)295Lbh/0 mice. L and M: Unusually strong nidogen staining of the GBM of peripheral capillary loops in both mildly and severely affected Cd151^tm1Nki/Cd151^tm1Nki kidneys (arrowheads). Note the extracapillary accumulation of nidogen (arrow) and massive capillary collapse (Beta1 staining) in the severely affected kidneys. O: Nidogen also accumulates in the capsular space of Itga3^tm1Son/Itga3^tm1Son Tg(NPHS2-cre)295Lbh/0 mice (arrow). Glomeruli are not collapsed, but show an abnormally thick GBM (arrowhead) with protrusions (open arrow). P-T: Posocin is present along the glomerular tuft in wild-type, mildly affected Cd151^tm1Nki/Cd151^tm1Nki and Itga3^tm1Son/Itga3⁺ Tg(NPHS2-cre)295Lbh/0 mice, but absent in severely affected Cd151^tm1Nki/Cd151^tm1Nki and Itga3^tm1Son/Itga3^tm1Son Tg(NPHS2-cre)295Lbh/0 mice. Staining of laminin-10 shows sclerosed glomeruli in Cd151^tm1Nki/Cd151^tm1Nki (R) and GBM thickening (arrowhead) with protrusions (open arrow) in Itga3^tm1Son/Itga3^tm1Son Tg(NPHS2-cre)295Lbh/0 mice (T). U-W: Nephrin is lost in some glomeruli of mildly affected Cd151^tm1Nki/Cd151^tm1Nki mice, but in all glomeruli of the severely affected Cd151^tm1Nki/Cd151^tm1Nki mice. There is massive up-regulation of the collagen alpha2 (IV) in the severe Cd151^tm1Nki/Cd151^tm1Nki phenotype (W) which is further characterized by hypercellularity in both the interstitium and glomeruli (C,H,M,R, and W; blue channel). X and Y: Nephrin is also reduced in Itga3^tm1Son/Itga3^tm1Son Tg(NPHS2-cre)295Lbh/0 mice as compared with the conditional heterozygote, whereas the collagen alpha2 (IV) is hardly up-regulated. Insets K-O, green channel (nidogen); Inset T, red channel (laminin-10). Bar: 50 um.

Copyright

This image is from Sachs N, J Cell Biol 2006 Oct 9;175(1):33-9, and is displayed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported License. J:114988

Associated Alleles

Symbol	Name
Cd151^tm1Nki	CD151 antigen; targeted mutation 1, The Netherlands Cancer Institute
Itga3^tm1Son	integrin alpha 3; targeted mutation 1, Arnaud Sonnenberg
Tg(NPHS2-cre)295Lbh	transgene insertion 295, Lawrence B Holzman

Associated Genotypes

Allelic Composition	Genetic Background
Cd151^tm1Nki/Cd151^tm1Nki	involves: 129P2/OlaHsd * FVB/N
Itga3^tm1Son/Itga3^tm1Son Tg(NPHS2-cre)295Lbh/0	Not Specified