CLDN16
| Claudin 16 | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Identifiers | |||||||||||||
| Symbols | CLDN16; HOMG3; PCLN1 | ||||||||||||
| External IDs | OMIM: 603959 MGI: 2148742 HomoloGene: 4799 GeneCards: CLDN16 Gene | ||||||||||||
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| RNA expression pattern | |||||||||||||
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| More reference expression data | |||||||||||||
| Orthologs | |||||||||||||
| Species | Human | Mouse | |||||||||||
| Entrez | 10686 | 114141 | |||||||||||
| Ensembl | ENSG00000113946 | ENSMUSG00000038148 | |||||||||||
| UniProt | Q9Y5I7 | Q925N4 | |||||||||||
| RefSeq (mRNA) | NM_006580 | NM_053241 | |||||||||||
| RefSeq (protein) | NP_006571 | NP_444471 | |||||||||||
| Location (UCSC) | Chr 3: 190.04 – 190.13 Mb | Chr 16: 26.46 – 26.48 Mb | |||||||||||
| PubMed search | |||||||||||||
Claudin-16 is a protein that in humans is encoded by the CLDN16 gene.[1][2] 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 renal failure.[2]
Model organisms
| 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[3] |
| Citrobacter infection | Normal[4] |
| All tests and analysis from[5][6] |
Model organisms have been used in the study of CLDN16 function. A conditional knockout mouse line, called Cldn16tm1a(KOMP)Wtsi[7][8] 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.[9][10][11]
Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[5][12] Twenty five tests were carried out on homozygous mutant animals and one significant abnormality was observed: the mice displayed urolithiasis. [5]
References
- ↑ 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.
- ↑ 2.0 2.1 "Entrez Gene: CLDN16 claudin 16".
- ↑ "Salmonella infection data for Cldn16". Wellcome Trust Sanger Institute.
- ↑ "Citrobacter infection data for Cldn16". Wellcome Trust Sanger Institute.
- ↑ 5.0 5.1 5.2 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.
- ↑ Mouse Resources Portal, Wellcome Trust Sanger Institute.
- ↑ "International Knockout Mouse Consortium".
- ↑ "Mouse Genome Informatics".
- ↑ 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.
- ↑ Dolgin E (2011). "Mouse library set to be knockout". Nature 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
- ↑ 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.
- ↑ 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.
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.
- 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.
- 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.
- 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.
- 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. 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.