Missense Mutations in the MIP Gene, Encoding the Major Intrinsic Protein of the Lens (Aquaporin-0), Underlie Cataracts in Humans

2000 ◽  
pp. 205-208
Author(s):  
Peter J. Francis ◽  
Vanita Berry ◽  
Shalesh Kaushal ◽  
Anthony T. Moore ◽  
Shomi Bhattacharya
Keyword(s):  
Missense Mutations ◽  
Major Intrinsic Protein ◽  
Gene Encoding ◽  
Intrinsic Protein

A Novel Missense Mutation in the Gene Encoding Major Intrinsic Protein (MIP) in a Giant Panda with Unilateral Cataract Formation

2020 ◽  
Author(s):  
Chao Bai ◽  
Yuyan You ◽  
Xuefeng Liu ◽  
Maohua Xia ◽  
Wei Wang ◽  
...  
Keyword(s):  
Missense Mutation ◽  
Conformational Changes ◽  
Giant Panda ◽  
Ailuropoda Melanoleuca ◽  
Major Intrinsic Protein ◽  
Gene Encoding ◽  
Functional Candidate Gene ◽  
Intrinsic Protein ◽  
Age Related ◽  
Unilateral Cataract

Abstract Background: Cataracts are defects of the lens that cause progressive visual impairment and ultimately blindness in many vertebrate species. Most cataracts are age-related, but up to one third have an underlying genetic cause. Cataracts are common in captive zoo animals, but it is often unclear whether these are congenital or acquired (age-related) lesions. Results: Here we used a functional candidate gene screening approach to identify mutations associated with cataracts in a captive giant panda (Ailuropoda melanoleuca). We screened 11 genes often associated with human cataracts and identified a novel missense mutation (c.686G>A) in the MIP gene encoding major intrinsic protein. This is expressed in the lens and normally accumulates in the plasma membrane of lens fiber cells, where it plays an important role in fluid transport and cell adhesion. The mutation causes the replacement of serine with asparagine (p.S229N) in the C-terminal tail of the protein, and modeling predicts that the mutation induces conformational changes that may interfere with lens permeability and cell–cell interactions.Conclusion: The c.686G>A mutation was found in a captive giant panda with a unilateral cataract but not in 18 controls from diverse regions in China, suggesting it is most likely a genuine disease-associated mutation rather than a single-nucleotide polymorphism. The mutation could therefore serve as a new genetic marker to predict the risk of congenital cataracts in captive giant pandas.

scholarly journals A novel missense mutation in the gene encoding major intrinsic protein (MIP) in a Giant panda with unilateral cataract formation

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Chao Bai ◽  
Yuyan You ◽  
Xuefeng Liu ◽  
Maohua Xia ◽  
Wei Wang ◽  
...  
Keyword(s):  
Missense Mutation ◽  
Conformational Changes ◽  
Giant Panda ◽  
Ailuropoda Melanoleuca ◽  
Major Intrinsic Protein ◽  
Gene Encoding ◽  
Functional Candidate Gene ◽  
Intrinsic Protein ◽  
Age Related ◽  
Unilateral Cataract

Abstract Background Cataracts are defects of the lens that cause progressive visual impairment and ultimately blindness in many vertebrate species. Most cataracts are age-related, but up to one third have an underlying genetic cause. Cataracts are common in captive zoo animals, but it is often unclear whether these are congenital or acquired (age-related) lesions. Results Here we used a functional candidate gene screening approach to identify mutations associated with cataracts in a captive giant panda (Ailuropoda melanoleuca). We screened 11 genes often associated with human cataracts and identified a novel missense mutation (c.686G > A) in the MIP gene encoding major intrinsic protein. This is expressed in the lens and normally accumulates in the plasma membrane of lens fiber cells, where it plays an important role in fluid transport and cell adhesion. The mutation causes the replacement of serine with asparagine (p.S229N) in the C-terminal tail of the protein, and modeling predicts that the mutation induces conformational changes that may interfere with lens permeability and cell–cell interactions. Conclusion The c.686G > A mutation was found in a captive giant panda with a unilateral cataract but not in 18 controls from diverse regions in China, suggesting it is most likely a genuine disease-associated mutation rather than a single-nucleotide polymorphism. The mutation could therefore serve as a new genetic marker to predict the risk of congenital cataracts in captive giant pandas.

scholarly journals A Novel Missense Mutation in the Gene Encoding Major Intrinsic Protein (MIP) in a Giant Panda with Cataracts

2020 ◽  
Author(s):  
Chao Bai ◽  
Yuyan You ◽  
Xuefeng Liu ◽  
Maohua Xia ◽  
Wei Wang ◽  
...  
Keyword(s):  
Missense Mutation ◽  
Conformational Changes ◽  
Giant Panda ◽  
Fluid Transport ◽  
Ailuropoda Melanoleuca ◽  
Major Intrinsic Protein ◽  
Gene Encoding ◽  
Functional Candidate Gene ◽  
Intrinsic Protein ◽  
Age Related

Abstract Background : Cataracts are defects of the lens that cause progressive visual impairment and ultimately blindness in many vertebrate species. Most cataracts are age-related, but up to one third have an underlying genetic cause. Cataracts are common in captive zoo animals, but it is often unclear whether these are congenital or sporadic (age-related) lesions.Results: Here we used a functional candidate gene-screening approach to identify mutations associated with cataracts in a captive giant panda ( Ailuropoda melanoleuca ). We identified a novel missense mutation ( c.686G>A) in the MIP gene encoding major intrinsic protein, which is expressed in the lens and normally accumulates in the plasma membrane of lens fiber cells, where it plays an important role in fluid transport and cell adhesion. The mutation causes the replacement of serine with asparagine ( p.229S>N ) in the C-terminal tail of the protein, and modeling revealed that mutation-induced conformational changes may interfere with lens permeability and cell–cell interactions.Conclusions: The mutation was not found in healthy pandas, suggesting it could serve as a new informative marker to predict the risk of congenital cataracts in captive giant pandas.

scholarly journals A Novel Missense Mutation in the Gene Encoding Major Intrinsic Protein (MIP) in a Giant Panda with Cataracts

2020 ◽  
Author(s):  
chao bai ◽  
Yuyan You ◽  
Xuefeng Liu ◽  
Maohua Xia ◽  
Wei Wang ◽  
...  
Keyword(s):  
Missense Mutation ◽  
Conformational Changes ◽  
Giant Panda ◽  
Fluid Transport ◽  
Ailuropoda Melanoleuca ◽  
Major Intrinsic Protein ◽  
Gene Encoding ◽  
Functional Candidate Gene ◽  
Intrinsic Protein ◽  
Age Related

Abstract Background: Cataracts are defects of the lens that cause progressive visual impairment and ultimately blindness in many vertebrate species. Most cataracts are age-related, but up to one third have an underlying genetic cause. Cataracts are common in captive zoo animals, but it is often unclear whether these are congenital or sporadic acquired (age-related) lesions. Results: Here we used a functional candidate gene- screening approach to identify mutations associated with cataracts in a captive giant panda (Ailuropoda melanoleuca). We screened 11 genes often associated with human cataracts and identified a novel missense mutation (c.686G>A) in the MIP gene encoding major intrinsic protein. , whichThis is expressed in the lens and normally accumulates in the plasma membrane of lens fiber cells, where it plays an important role in fluid transport and cell adhesion. The mutation causes the replacement of serine with asparagine (p.229S>Np.S229N) in the C-terminal tail of the protein, and modeling revealed predicts that the mutation- induced induces conformational changes that may interfere with lens permeability and cell–cell interactions. Conclusion: The c.686G>A mutation was found in a captive giant panda with a unilateral cataract but not in 18 controls from diverse regions of in China, suggesting that c.686G>Ait is likely to bemost likely a genuine disease-causing associated mutation rather than a single-nucleotide polymorphism 5 regions was used in this research. Conclusions: The c.686G>A mutation was not found in healthy pandas, suggesting itThe mutation could therefore serve as a new genetic marker to predict the risk of congenital cataracts in captive giant pandas.

Genome-wide Characterization of Major Intrinsic Protein (MIP) Gene Family in Brachypodium distachyon

2018 ◽  
Vol 13 (5) ◽  
pp. 536-552 ◽  
Author(s):  
Ankush Ashok Saddhe ◽  
Shweta ◽  
Kareem A. Mosa ◽  
Kundan Kumar ◽  
Manoj Prasad ◽  
...  
Keyword(s):  
Gene Family ◽  
Brachypodium Distachyon ◽  
Major Intrinsic Protein ◽  
Intrinsic Protein ◽  
Genome Wide

scholarly journals Missense mutations in theTGM2 gene encoding transglutaminase 2 are found in patients with early-onset type 2 diabetes

2007 ◽  
Vol 28 (11) ◽  
pp. 1150-1150 ◽  
Author(s):  
O. Porzio ◽  
O. Massa ◽  
V. Cunsolo ◽  
C. Colombo ◽  
M. Malaponti ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Early Onset ◽  
Transglutaminase 2 ◽  
Missense Mutations ◽  
Gene Encoding ◽  
Onset Type

scholarly journals Isolation of a gene encoding nodulin-like intrinsic protein of Escherichia coli

IUBMB Life ◽  
1997 ◽  
Vol 41 (5) ◽  
pp. 995-1003 ◽  
Author(s):  
Kiyohide Fushimi ◽  
Liqun Bai ◽  
Fumiaki Marumo ◽  
Sei Sasaki
Keyword(s):  
Escherichia Coli ◽  
Gene Encoding ◽  
Intrinsic Protein

scholarly journals Constitutive signaling by the C-terminal fragment of polycystin-1 is mediated by a tethered peptide agonist

2021 ◽  
Author(s):  
Brenda S Magenheimer ◽  
Ericka Nevarez Munoz ◽  
Jayalakshmi Ravichandran ◽  
Robin L Maser
Keyword(s):  
G Protein ◽  
Transmembrane Domain ◽  
Missense Mutations ◽  
Protein Signaling ◽  
Gene Encoding ◽  
Reporter Assays ◽  
Autosomal Dominant Polycystic Kidney ◽  
Signaling Activation ◽  
Peptide Agonist ◽  
Adhesion Gpcr

Mutation of the PKD1 gene, encoding polycystin-1 (PC1), is the primary cause of autosomal dominant polycystic kidney disease. PC1 is an 11-transmembrane domain protein that binds and modulates the activity of multiple heterotrimeric G protein families and is thought to function as a non-canonical G protein-coupled receptor (GPCR). PC1 shares a conserved GPCR autoproteolysis inducing (GAIN) domain with the adhesion family of GPCRs, that promotes an auto-catalytic, cis-cleavage at the GPCR proteolysis site (GPS) located proximal to the first transmembrane domain. GPS cleavage divides these receptors into two associated subunits, the extracellular N-terminal (NTF) and transmembrane C-terminal (CTF) fragments. For the adhesion GPCRs, removal of the NTF leads to activation of G protein signaling as a result of the exposure and subsequent intramolecular binding of the extracellular N-terminal stalk of the CTF, i.e., the tethered cryptic ligand or tethered agonist model. Here, we test the hypothesis that PC1-mediated signaling is regulated by an adhesion GPCR-like, tethered agonist mechanism. Using cell-based reporter assays and mutagenesis of PC1 expression constructs, we show that the CTF form of PC1 requires the stalk for signaling activation and synthetic peptides derived from the PC1 stalk sequence can re-activate signaling by a stalk-less CTF. In addition, we demonstrate that ADPKD-associated missense mutations within the PC1 stalk affect signaling and can inhibit GPS cleavage. These results provide a foundation for beginning to understand the molecular mechanism of G protein regulation by PC1 and suggest that a tethered agonist-mediated mechanism can contribute to PKD pathogenesis.

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