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C57BL/6JCya-Cubnem1flox/Cya
Common Name:
Cubn-flox
Product ID:
S-CKO-17516
Background:
C57BL/6JCya
Product Type
Age
Genotype
Sex
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Basic Information
Strain Name
Cubn-flox
Strain ID
CKOCMP-65969-Cubn-B6J-VC
Gene Name
Cubn
Product ID
S-CKO-17516
Gene Alias
D2Wsu88e
Background
C57BL/6JCya
NCBI ID
65969
Modification
Conditional knockout
Chromosome
2
Phenotype
MGI:1931256
Document
Click here to download >>
Application
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Rare Disease Data Center >>
Note
Note: When using this mouse strain in a publication, please cite “C57BL/6JCya-Cubnem1flox/Cya mice (Catalog S-CKO-17516) were purchased from Cyagen.”
Strain Description
Ensembl Number
ENSMUST00000091436
NCBI RefSeq
NM_001081084
Target Region
Exon 7~8
Size of Effective Region
~1.8 kb
Detailed Document
Click here to download >>
Overview of Gene Research
CUBN, encoding cubilin, is an important gene. Cubilin is an endocytic receptor highly expressed in renal proximal tubules, mediating the uptake of albumin, transferrin, and α1-microglobulin. It also serves as the intestinal receptor for the endocytosis of intrinsic factor-vitamin B12. Mutations in CUBN are associated with Imerslund-Gräsbeck syndrome (IGS), which is characterized by intestinal malabsorption of vitamin B12 and in some cases proteinuria [1,2,4,6].

Research has identified CUBN variants associated with various conditions. Biallelic pathogenic variants in the CUBN gene were associated with chronic isolated proteinuria and early childhood onset, with normal renal function. These proteinuria cases often had a high proportion of albuminuria, and unlike more N-terminal IGS mutations, many proteinuria-associated CUBN variants led to modifications or truncations after the vitamin B12-binding domain [1]. Some studies also found that CUBN gene mutations may cause isolated proteinuria pathologically presented as focal segmental glomerulosclerosis (FSGS) in children [2]. Novel variants after the vitamin B12-binding domain of CUBN were shown to disrupt the association with Amnionless (AMN), causing albuminuria without progressive glomerular filtration barrier impairment [3]. In addition, some CUBN missense variants were associated with higher levels of estimated glomerular filtration rate (eGFR) in non-diabetes populations [5].

In conclusion, CUBN plays a crucial role in renal albumin reabsorption and vitamin B12 uptake. Research on CUBN variants has provided insights into the complex relationship between proteinuria and renal function. Understanding the function of CUBN through these genetic findings helps in clarifying the mechanisms underlying certain kidney-related and vitamin B12-metabolism-related disorders.

References:
1. Bedin, Mathilda, Boyer, Olivia, Servais, Aude, Antignac, Corinne, Simons, Matias. . Human C-terminal CUBN variants associate with chronic proteinuria and normal renal function. In The Journal of clinical investigation, 130, 335-344. doi:10.1172/JCI129937. https://pubmed.ncbi.nlm.nih.gov/31613795/
2. Yang, Jing, Xu, Yongli, Deng, Linxia, Zhang, Yu, Zhou, Jianhua. 2022. CUBN gene mutations may cause focal segmental glomerulosclerosis (FSGS) in children. In BMC nephrology, 23, 15. doi:10.1186/s12882-021-02654-x. https://pubmed.ncbi.nlm.nih.gov/34979989/
3. Gan, Chun, Zhou, Xindi, Chen, Dan, Jiang, Wei, Li, Qiu. 2022. Novel pathogenic variants in CUBN uncouple proteinuria from renal function. In Journal of translational medicine, 20, 480. doi:10.1186/s12967-022-03706-y. https://pubmed.ncbi.nlm.nih.gov/36266725/
4. Falcon, Corey, Hamm, Austin J, Li, Geling, Howard, Thomas H, Xavier, Ana C. . Novel CUBN Mutation in a Young Child With Megaloblastic Anemia. In Journal of pediatric hematology/oncology, 43, e546-e549. doi:10.1097/MPH.0000000000001958. https://pubmed.ncbi.nlm.nih.gov/33031161/
5. Uglebjerg, Nicoline, Ahmadizar, Fariba, Aly, Dina M, Rossing, Peter, Ahluwalia, Tarunveer S. 2023. Four missense genetic variants in CUBN are associated with higher levels of eGFR in non-diabetes but not in diabetes mellitus or its subtypes: A genetic association study in Europeans. In Frontiers in endocrinology, 14, 1081741. doi:10.3389/fendo.2023.1081741. https://pubmed.ncbi.nlm.nih.gov/36926036/
6. Yang, Huihui, He, Lanfen, Gong, Hongjian, Liao, Panli, Wang, Xiaowen. . Identification of novel pathogenic variants of CUBN in patients with isolated proteinuria. In Molecular genetics & genomic medicine, 12, e2353. doi:10.1002/mgg3.2353. https://pubmed.ncbi.nlm.nih.gov/38488435/
Quality Control Standard
Sperm Test

Pre-cryopreservation: Measurement of sperm concentration, determination of sperm viability.

Post-cryopreservation: A vial of cryopreserved sperms is selected for in-vitro fertilization from each batch.

Environmental Standards:SPF
Available Region:Global
Source:Cyagen
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