A Patient with Cubilin Deficiency

Storm, Tina; Emma, Francesco; Verroust, P; Hertz, Jens Michael; Nielsen, Rikke; Christensen, Erik

doi:10.1056/nejmc1009804

Cited by 59 publications

(66 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…An inverse situation was recently reported where the altered interdependency of both proteins was due to a CUBN mutation in exon 23 and no mutation in AMN. 24 In conclusion, we report a case of IGS with compound heterozygous mutations on AMN which indicates that amnionless is essential for the luminal expression of cubilin in humans. …”

Section: Resultsmentioning

confidence: 99%

Luminal expression of cubilin is impaired in Imerslund-Grasbeck syndrome with compound AMN mutations in intron 3 and exon 7

Namour¹,

Dobrovoljski²,

Chéry³

et al. 2011

Haematologica

View full text Add to dashboard Cite

Section: Resultsmentioning

confidence: 99%

Luminal expression of cubilin is impaired in Imerslund-Grasbeck syndrome with compound AMN mutations in intron 3 and exon 7

Namour¹,

Dobrovoljski²,

Chéry³

et al. 2011

Haematologica

View full text Add to dashboard Cite

“…We also identified other Drosophila genes with human homologs that have been linked to renal diseases, including two novel Drosophila genes CG11592 and CG32702, which encode two renal disease genes Amnionless and Cubilin, 25,26 respectively. Together with the slit diaphragm genes, these results strongly suggested that Drosophila nephrocytes can be modeled to study known nephrotic syndrome-associated genes and identify novel genes potentially involved in kidney diseases.…”

mentioning

confidence: 99%

An In Vivo Functional Analysis System for Renal Gene Discovery in Drosophila Pericardial Nephrocytes

Zhang¹,

Zhao²,

Han

2013

Journal of the American Society of Nephrology

100

135

View full text Add to dashboard Cite

The difficulty in accessing mammalian nephrons in vivo hinders the study of podocyte biology. The Drosophila nephrocyte shares remarkable similarities to the glomerular podocyte, but the lack of a functional readout for nephrocytes makes it challenging to study this model of the podocyte, which could potentially harness the power of Drosophila genetics. Here, we present a functional analysis of nephrocytes and establish an in vivo system to screen for renal genes. We found that nephrocytes efficiently take up secreted fluorescent protein, and therefore, we generated a transgenic line carrying secreted fluorescent protein and combined it with a nephrocyte-specific driver for targeted gene knockdown, allowing the identification of genes required for nephrocyte function. To validate this system, we examined the effects of knocking down sns and duf, the Drosophila homologs of nephrin and Neph1, respectively, in pericardial nephrocytes. Knockdown of sns or duf completely abolished the accumulation of the fluorescent protein in pericardial nephrocytes. Examining the ultrastructure revealed that the formation of the nephrocyte diaphragm and lacunar structure, which is essential for protein uptake, requires sns. Our preliminary genetic screen also identified Mec2, which encodes the homolog of mammalian Podocin. Taken together, these data suggest that the Drosophila pericardial nephrocyte is a useful in vivo model to help identify genes involved in podocyte biology and facilitate the discovery of renal disease genes.

show abstract

“…Vitamin B 12 (B 12 ) is a water-soluble vitamin that plays a key role in the normal function of the nervous system and blood formation along with serving as a cofactor for the formation of methionine from homocysteine [11]. Normally, B 12 is released from dietary protein in the stomach and binds to intrinsic factor (IF).…”

Section: Discussionmentioning

confidence: 99%

“…Normally, B 12 is released from dietary protein in the stomach and binds to intrinsic factor (IF). The B 12 -IF complex is absorbed in the ileum via the cubilin receptor [11]. Defects in cubilin, a proximal tubular membrane protein, have been associated with both megaloblastic anemia and tubular proteinuria [11][12][13][14].…”

Section: Discussionmentioning

confidence: 99%