A new recurrent chromosomal translocation t(3;11)(q13;q14) in myelodysplastic syndromes associated with overexpression of the ILDR1 gene

Zagaria, Antonella; Anelli, Luisa; Coccaro, Nicoletta; Casieri, Paola; Minervini, Angela; Buttiglione, Valentina; Ricco, Alessandra; Specchia, Giorgina; Albano, Francesco

doi:10.1016/j.leukres.2012.01.026

Cited by 7 publications

(4 citation statements)

References 23 publications

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“…ILDR1 shows approximately 30% homology to lipolysis stimulated receptor, and there is evidence that ILDR1 plays a role in mediating fat-stimulated cholecystokinin secretion ( Hauge et al, 2004 ; Chandra et al, 2013 ). In addition, overexpression of ILDR1 might have biological implications in myelodysplastic syndromes ( Zagaria et al, 2012 ).…”

Section: Introductionmentioning

confidence: 99%

ILDR1 deficiency causes degeneration of cochlear outer hair cells and disrupts the structure of the organ of Corti: a mouse model for human DFNB42

Sang

et al. 2015

Biology Open

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Immunoglobulin-like domain containing receptor 1 (ILDR1) is a poorly characterized gene that was first identified in lymphoma cells. Mutations in ILDR1 are responsible for DFNB42, but the pathogenesis of hearing loss caused by ILDR1 mutations remains to be elucidated. To explore the role of ILDR1 in hearing, we created Ildr1 knockout mice. In heterozygous mice, ILDR1 expression was found in outer hair cells (OHCs) and inner hair cells (IHCs) of the organ of Corti. ILDR1-deficient mice are profoundly deaf by postnatal day 21 (P21). No significant difference was observed in the supporting cells and IHCs of ILDR1-deficient mice, but progressive degeneration of OHCs occurred at P15 and disruption of the tunnel running through the organ of Corti was noticeable at P21. By P28, there were no OHCs visible in any of the turns of the organ of Corti, and the tunnel of the organ of Corti was entirely destroyed. ILDR1 deficiency affects expression of tricellulin in vivo, and this provides a possible explanation to hearing loss. To further elucidate the mechanism of deafness related to ILDR1 deficiency, we pursued a differential proteomic approach to comprehensively assess differential protein expression in the cochleae of Ildr1+/− and Ildr1−/− mice at P21. Altogether, 708 proteins were up-regulated (fold change >1.5) and 114 proteins were down-regulated (fold change <0.5) in the Ildr1−/− mice compared with Ildr1+/− mice. Gene ontology classification indicated that a number of differentially expressed proteins are involved in cell adhesion, protein and vesicle-mediated transport, cell death, membrane organization, and cellular homeostasis. A few of these proteins are closely related to hearing development. Taken together, our data suggest that ILDR1 is important for the survival of OHCs and provide novel insights into the pathogenesis of human deafness DFNB42 deafness.

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Section: Introductionmentioning

confidence: 99%

ILDR1 deficiency causes degeneration of cochlear outer hair cells and disrupts the structure of the organ of Corti: a mouse model for human DFNB42

Sang

et al. 2015

Biology Open

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“…The major isoforms of both ILDR1 and ILDR3 localize either to the plasma membrane (PM) or to the cytosol [3], [4]. Although ILDR1 has been linked to neoplastic disease 2 [5] and non-syndromic deafness [6], how it functions is unknown. ILDR3, which was initially identified as a fatty acid-activated, liver-specific lipoprotein receptor [7], has since been characterized variously as a receptor for Clostridium toxin [8], as an hepatic receptor upregulated by leptin [9] and as a component of tri-cellular junctions in epithelial cells [10].…”

Section: Introductionmentioning

confidence: 99%

ILDR2: An Endoplasmic Reticulum Resident Molecule Mediating Hepatic Lipid Homeostasis

et al. 2013

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Ildr2, a modifier of diabetes susceptibility in obese mice, is expressed in most organs, including islets and hypothalamus, with reduced levels in livers of diabetes-susceptible B6.DBA mice congenic for a 1.8 Mb interval of Chromosome 1. In hepatoma and neuronal cells, ILDR2 is primarily located in the endoplasmic reticulum membrane. We used adenovirus vectors that express shRNA or are driven by the CMV promoter, respectively, to knockdown or overexpress Ildr2 in livers of wild type and ob/ob mice. Livers in knockdown mice were steatotic, with increased hepatic and circulating triglycerides and total cholesterol. Increased circulating VLDL, without reduction in triglyceride clearance suggests an effect of reduced hepatic ILDR2 on hepatic cholesterol clearance. In animals that overexpress Ildr2, hepatic triglyceride and total cholesterol levels were reduced, and strikingly so in ob/ob mice. There were no significant changes in body weight, energy expenditure or glucose/insulin homeostasis in knockdown or overexpressing mice. Knockdown mice showed reduced expression of genes mediating synthesis and oxidation of hepatic lipids, suggesting secondary suppression in response to increased hepatic lipid content. In Ildr2-overexpressing ob/ob mice, in association with reduced liver fat content, levels of transcripts related to neutral lipid synthesis and cholesterol were increased, suggesting “relief” of the secondary suppression imposed by lipid accumulation. Considering the fixed location of ILDR2 in the endoplasmic reticulum, we investigated the possible participation of ILDR2 in ER stress responses. In general, Ildr2 overexpression was associated with increases, and knockdown with decreases in levels of expression of molecular components of canonical ER stress pathways. We conclude that manipulation of Ildr2 expression in liver affects both lipid homeostasis and ER stress pathways. Given these reciprocal interactions, and the relatively extended time-course over which these studies were conducted, we cannot assign causal primacy to either the effects on hepatic lipid homeostasis or ER stress responses.

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“…Relative to other genes, ILDR1 has been less investigated in other diseases, including cancers. Zagaria revealed that ILDR1 is overexpressed due to a rare recurrent chromosomal translocation (3; 11) (q13; q14) in two patients with myelodysplastic syndromes [ 11 ]. Emami NC conducted an integrated study of prostate cancer genetic etiology and confirmed that ILDR1 is highly expressed in prostate tissue and related to the B7/CD28 family of T cell immune checkpoint markers [ 12 ].…”

Section: Discussionmentioning

confidence: 99%

“…In addition, ILDR1 can mediate the secretion of cholecystokinin secretion through a mechanism that is dependent on fatty acids and lipoproteins [ 10 ]. The gene has been shown to be overexpressed in some tumor diseases and may be involved in the formation and development of tumors [ 11 , 12 ]. These previous studies indicate that ILDR1 may function as a multimeric receptor on the cell surface and that the expression of this gene may be a diagnostic marker for cancer progression.…”

Section: Introductionmentioning

confidence: 99%

Analyses of the expression and prognosis of ILDR1 in human gastric cancer

Wang¹,

Zhai²,

Song

2022

Heliyon

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A new recurrent chromosomal translocation t(3;11)(q13;q14) in myelodysplastic syndromes associated with overexpression of the ILDR1 gene

Cited by 7 publications

References 23 publications

ILDR1 deficiency causes degeneration of cochlear outer hair cells and disrupts the structure of the organ of Corti: a mouse model for human DFNB42

ILDR1 deficiency causes degeneration of cochlear outer hair cells and disrupts the structure of the organ of Corti: a mouse model for human DFNB42

ILDR2: An Endoplasmic Reticulum Resident Molecule Mediating Hepatic Lipid Homeostasis

Analyses of the expression and prognosis of ILDR1 in human gastric cancer

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