CLDN16

CLDN16
Identifiers
Aliases	CLDN16 , HOMG3, PCLN1, claudin 16
External IDs	OMIM: 603959 MGI: 2148742 HomoloGene: 4799 GeneCards: CLDN16
Gene location (Human) Chr. Chromosome 3 (human) [1] Band 3q28 Start 190,322,541 bp [1] End 190,412,138 bp [1]
Gene location (Mouse) Chr. Chromosome 16 (mouse) [2] Band 16|16 B2 Start 26,463,135 bp [2] End 26,482,765 bp [2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • magnesium ion transmembrane transporter activity • GO:0001948 protein binding • structural molecule activity • identical protein binding Cellular component • integral component of membrane • cell junction • plasma membrane • membrane • bicellular tight junction Biological process • excretion • calcium-independent cell-cell adhesion via plasma membrane cell-adhesion molecules • ion transport • cellular metal ion homeostasis • magnesium ion transmembrane transport Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	10686	114141
Ensembl	ENSG00000113946	ENSMUSG00000038148
UniProt	Q9Y5I7	Q925N4
RefSeq (mRNA)	NM_006580 NM_001378492 NM_001378493	NM_053241
RefSeq (protein)	NP_006571 NP_001365421 NP_001365422	NP_444471
Location (UCSC)	Chr 3: 190.32 – 190.41 Mb	Chr 16: 26.46 – 26.48 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

Claudin-16 is a protein that in humans is encoded by the CLDN16 gene. ^{[5] [6]} It belongs to the group of claudins.

Tight junctions represent one mode of cell-to-cell adhesion in epithelial or endothelial cell sheets, forming continuous seals around cells and serving as a physical barrier to prevent solutes and water from passing freely through the paracellular space. These junctions are composed of sets of continuous networking strands in the outwardly facing cytoplasmic leaflet, with complementary grooves in the inwardly facing extracytoplasmic leaflet. The protein encoded by this gene, a member of the claudin family, is an integral membrane protein and a component of tight junction strands. It is found primarily in the kidneys, specifically in the thick ascending limb of Henle, where it acts as either an intercellular pore or ion concentration sensor to regulate the paracellular resorption of magnesium ions. Defects in this gene are a cause of primary hypomagnesemia, which is characterized by massive renal magnesium wasting with hypomagnesemia and hypercalciuria, resulting in nephrocalcinosis and kidney failure. ^[6]

Model organisms

Cldn16 knockout mouse phenotype

Characteristic	Phenotype
Homozygote viability	Normal
Fertility	Normal
General Observations	Abnormal
Body weight	Normal
Anxiety	Normal
Neurological assessment	Normal
Grip strength	Normal
Hot plate	Normal
Dysmorphology	Normal
Indirect calorimetry	Normal
Glucose tolerance test	Normal
Auditory brainstem response	Normal
DEXA	Normal
Radiography	Normal
Body temperature	Normal
Eye morphology	Normal
Clinical chemistry	Normal
Haematology	Normal
Peripheral blood lymphocytes	Normal
Micronucleus test	Normal
Heart weight	Normal
Brain histopathology	Normal
Eye Histopathology	Normal
Salmonella infection	Normal [7]
Citrobacter infection	Normal [8]
All tests and analysis from [9] [10]

Model organisms have been used in the study of CLDN16 function. A conditional knockout mouse line, called Cldn16^{tm1a(KOMP)Wtsi [11] [12]} was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists. ^{[13] [14] [15]}

Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. ^{[9] [16]} Twenty five tests were carried out on homozygous mutant animals and one significant abnormality was observed: the mice displayed urolithiasis. ^[9]

References

1. GRCh38: Ensembl release 89: ENSG00000113946 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000038148 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Simon DB, Lu Y, Choate KA, Velazquez H, Al-Sabban E, Praga M, Casari G, Bettinelli A, Colussi G, Rodriguez-Soriano J, McCredie D, Milford D, Sanjad S, Lifton RP (Jul 1999). "Paracellin-1, a renal tight junction protein required for paracellular Mg2+ resorption". Science. 285 (5424): 103–6. doi:10.1126/science.285.5424.103. PMID   10390358.
6. "Entrez Gene: CLDN16 claudin 16".
7. "Salmonella infection data for Cldn16". Wellcome Trust Sanger Institute.
8. "Citrobacter infection data for Cldn16". Wellcome Trust Sanger Institute.
9. Gerdin AK (2010). "The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice". Acta Ophthalmologica. 88: 925–7. doi:10.1111/j.1755-3768.2010.4142.x. S2CID   85911512.
10. Mouse Resources Portal, Wellcome Trust Sanger Institute.
11. "International Knockout Mouse Consortium".
12. "Mouse Genome Informatics".
13. Skarnes, W. C.; Rosen, B.; West, A. P.; Koutsourakis, M.; Bushell, W.; Iyer, V.; Mujica, A. O.; Thomas, M.; Harrow, J.; Cox, T.; Jackson, D.; Severin, J.; Biggs, P.; Fu, J.; Nefedov, M.; De Jong, P. J.; Stewart, A. F.; Bradley, A. (2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature. 474 (7351): 337–342. doi:10.1038/nature10163. PMC   3572410 . PMID   21677750.
14. Dolgin E (2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi: 10.1038/474262a . PMID   21677718.
15. Collins FS, Rossant J, Wurst W (2007). "A Mouse for All Reasons". Cell. 128 (1): 9–13. doi: 10.1016/j.cell.2006.12.018 . PMID   17218247. S2CID   18872015.
16. van der Weyden L, White JK, Adams DJ, Logan DW (2011). "The mouse genetics toolkit: revealing function and mechanism". Genome Biol. 12 (6): 224. doi:10.1186/gb-2011-12-6-224. PMC   3218837 . PMID   21722353.

External links

• Human CLDN16 genome location and CLDN16 gene details page in the UCSC Genome Browser .

Further reading

• Kniesel U, Wolburg H (2000). "Tight junctions of the blood–brain barrier". Cell. Mol. Neurobiol. 20 (1): 57–76. doi:10.1023/A:1006995910836. PMID   10690502. S2CID   26473781.
• Heiskala M, Peterson PA, Yang Y (2001). "The roles of claudin superfamily proteins in paracellular transport". Traffic. 2 (2): 93–8. doi: 10.1034/j.1600-0854.2001.020203.x . PMID   11247307. S2CID   12132159.
• Tsukita S, Furuse M, Itoh M (2001). "Multifunctional strands in tight junctions". Nat. Rev. Mol. Cell Biol. 2 (4): 285–93. doi:10.1038/35067088. PMID   11283726. S2CID   36524601.
• Tsukita S, Furuse M (2003). "Claudin-based barrier in simple and stratified cellular sheets". Curr. Opin. Cell Biol. 14 (5): 531–6. doi:10.1016/S0955-0674(02)00362-9. PMID   12231346.
• González-Mariscal L, Betanzos A, Nava P, Jaramillo BE (2003). "Tight junction proteins". Prog. Biophys. Mol. Biol. 81 (1): 1–44. doi: 10.1016/S0079-6107(02)00037-8 . PMID   12475568.
• Manz F, Schärer K, Janka P, Lombeck J (1978). "Renal magnesium wasting, incomplete tubular acidosis, hypercalciuria and nephrocalcinosis in siblings". Eur. J. Pediatr. 128 (2): 67–79. doi:10.1007/BF00496992. PMID   668721. S2CID   11806270.
• Weber S, Hoffmann K, Jeck N, et al. (2000). "Familial hypomagnesaemia with hypercalciuria and nephrocalcinosis maps to chromosome 3q27 and is associated with mutations in the PCLN-1 gene". Eur. J. Hum. Genet. 8 (6): 414–22. doi: 10.1038/sj.ejhg.5200475 . PMID   10878661.
• Weber S, Schneider L, Peters M, et al. (2001). "Novel paracellin-1 mutations in 25 families with familial hypomagnesemia with hypercalciuria and nephrocalcinosis". J. Am. Soc. Nephrol. 12 (9): 1872–81. doi:10.1681/ASN.V1291872. PMID   11518780.
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi: 10.1073/pnas.242603899 . PMC   139241 . PMID   12477932.
• Müller D, Kausalya PJ, Claverie-Martin F, et al. (2004). "A Novel Claudin 16 Mutation Associated with Childhood Hypercalciuria Abolishes Binding to ZO-1 and Results in Lysosomal Mistargeting". Am. J. Hum. Genet. 73 (6): 1293–301. doi:10.1086/380418. PMC   1180395 . PMID   14628289.
• Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC   528928 . PMID   15489334.
• Hou J, Paul DL, Goodenough DA (2005). "Paracellin-1 and the modulation of ion selectivity of tight junctions". J. Cell Sci. 118 (Pt 21): 5109–18. doi: 10.1242/jcs.02631 . PMID   16234325.
• Kausalya PJ, Amasheh S, Günzel D, et al. (2006). "Disease-associated mutations affect intracellular traffic and paracellular Mg2+ transport function of Claudin-16". J. Clin. Invest. 116 (4): 878–91. doi:10.1172/JCI26323. PMC   1395478 . PMID   16528408.
• Türkmen M, Kasap B, Soylu A, et al. (2007). "Paracellin-1 gene mutation with multiple congenital abnormalities". Pediatr. Nephrol. 21 (11): 1776–8. doi:10.1007/s00467-006-0247-7. PMID   16924549. S2CID   9410376.
• Liu F, Koval M, Ranganathan S, Fanayan S, Hancock WS, Lundberg EK, Beavis RC, Lane L, Duek P, McQuade L, Kelleher NL, Baker MS (2015). "A systems proteomics view of the endogenous human claudin protein family". J Proteome Res. 15 (2): 339–359. doi:10.1021/acs.jproteome.5b00769. PMC   4777318 . PMID   26680015.