A 76-bp Deletion in the Mip Gene Causes Autosomal Dominant Cataract in Hfi Mice

Sidjanin, D. J.; Parker-Wilson, Devonne M.; Neuhäuser-Klaus, A.; Pretsch, Walter; Favor, Jack; Deen, Peter M.T.; Ohtaka-Maruyama, Chiaki; Lu, Yun; Bragin, Alvina; Skach, William R.; Chepelinsky, Ana B.; Grimes, Patricia A.; Stambolian, Dwight

doi:10.1006/geno.2001.6509

Cited by 38 publications

(40 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Among the lens membrane proteins, MP20 (also referred to as MP19 and encoded by the gene Lim2), MP26 and MP70 [also referred to as gap junction subunit a8 or connexin50 (Cx50)] are the most important ones. Mutations in all the corresponding genes have been reported to lead to dominant cataracts in mouse (Shiels and Bassnett, 1996;Steele et al, 1998;Sidjanin et al, 2001) and man (Shiels et al, 1998;Berry et al, 2000). Here a second mutant allele of the MP70/Cx50 encoding gene Gja8 is reported in the mouse, which exhibits a dominant nuclear and zonular cataract.…”

Section: Introductionmentioning

confidence: 94%

Characterization of a Mutation in the Lens-specific MP70 Encoding Gene of the Mouse Leading to a Dominant Cataract

Graw

Löster

Soewarto

et al. 2001

Experimental Eye Research

View full text Add to dashboard Cite

Section: Introductionmentioning

confidence: 94%

Characterization of a Mutation in the Lens-specific MP70 Encoding Gene of the Mouse Leading to a Dominant Cataract

Graw

Löster

Soewarto

et al. 2001

Experimental Eye Research

View full text Add to dashboard Cite

“…3) in the translated MIP product (Okamura et al 2003). The MIP/AQP0 gene mutations involving deletions are reflected in the size of the MIP/AQP0 transcript without affecting the efficiency of transcription (Shiels and Griffin 1993;Sidjanin et al 2001). However, the main effect of the four MIP/AQP0 gene mutations is on the fate of the translated product at the endoplasmic reticulum.…”

Section: Mip/aqp0 Gene Mutations In Micementioning

confidence: 98%

“…However, the main effect of the four MIP/AQP0 gene mutations is on the fate of the translated product at the endoplasmic reticulum. In the four mouse MIP mutants indicated in Table 1, the translated product of the mutant MIP gene is retained in the endoplasmic reticulum, thereby preventing the insertion of the defective protein in the plasma membrane (Okamura et al 2003;Shiels and Bassnett 1996;Shiels et al 2000;Sidjanin et al 2001). Membrane proteins forming multimers oligomerize at the endoplasmic reticulum.…”

Section: Mip/aqp0 Gene Mutations In Micementioning

confidence: 99%

“…Mouse Hfi (Hydropic lens) (Sidjanin et al 2001) Deletion 76 H5 domains and loop D, shown in Fig. 3) are deleted in the translated MIP product (Sidjanin et al 2001).…”

Section: Mip/aqp0 Gene Mutations In Micementioning

confidence: 99%

“…3) are deleted in the translated MIP product (Sidjanin et al 2001). The Cat Tohm (Tohoku) cataract, caused by a 12-base pair deletion in MIP/AQP0 exon 1 without changing the reading frame, results in deletion of four amino acids (amino acids 46-49 in transmembrane domain H2, shown in Fig.…”

Section: Mip/aqp0 Gene Mutations In Micementioning

confidence: 99%

See 2 more Smart Citations

Structural Function of MIP/Aquaporin 0 in the Eye Lens; Genetic Defects Lead to Congenital Inherited Cataracts

Chepelinsky

Handbook of Experimental Pharmacology

Self Cite

View full text Add to dashboard Cite

Aquaporin 0 (AQP0) was originally characterized as a membrane intrinsic protein, specifically expressed in the lens fibers of the ocular lens and designated MIP, for major intrinsic protein of the lens. Once the gene was cloned, an internal repeat was identified, encoding for the amino acids Asp-Pro-Ala, the NPA repeat. Shortly, the MIP gene family was emerging, with members being characterized in mammals, insects, and plants. Once Peter Agre's laboratory developed a functional assay for water channels, the MIP family became the aquaporin family and MIP became known as aquaporin 0. Besides functioning as a water channel, aquaporin 0 also plays a structural role, being required for maintaining the transparency and optical accommodation of the ocular lens. Mutations in the AQP0 gene in human and mice result in genetic cataracts; deletion of the MIP/AQP0 gene in mice results in lack of suture formation required for maintenance of the lens fiber architecture, resulting in perturbed accommodation and focus properties of the ocular lens. Crystallography studies support the notion of the double function of aquaporin 0 as a water channel (open configuration) or adhesion molecule (closed configuration) in the ocular lens fibers. The functions of MIP/AQP0, both as a water channel and an adhesive molecule in the lens fibers, contribute to the narrow intercellular space of the lens fibers that is required for lens transparency and accommodation.

show abstract

A novel single‐base deletional mutation of MIP impairs protein distribution and cell‐to‐cell adhesion in autosomal dominant cataracts in a Chinese family

Yu,

Qiao,

et al. 2023

American J of Med Genetics Pt A

View full text Add to dashboard Cite

Congenital cataracts are the leading cause of irreversible visual disability in children, and genetic factors play an important role in their development. In this study, targeted exome sequencing revealed a novel single‐base deletional mutation of MIP (c.301delG; p.Ala101Profs*16) segregated with congenital punctate cataract in a Chinese family. The hydrophobic properties, and secondary and tertiary structures for truncated MIP were predicted to affect the function of protein by bioinformatics analysis. When MIP‐WT and MIP‐Ala101fs expression constructs were singly transfected into HeLa cells, it was found that the mRNA level showed no significant difference, while the protein level of the mutant was remarkably reduced compared to that of the wild‐type MIP. Immunofluorescence images showed that the MIP‐WT was principally localized to the plasma membrane, whereas the MIP‐Ala101fs protein was aberrantly trapped in the cytoplasm. Furthermore, the cell‐to‐cell adhesion capability and the cell‐to‐cell communication property were both significantly reduced for MIP‐Ala101fs compared to the MIP‐WT (all *p < 0.05). This is the first report of the c.301delG mutation in the MIP gene associated with autosomal dominant congenital cataracts. We propose that the cataract is caused by the decreased protein expression and reduced cell‐to‐cell adhesion by the mutant MIP. The impaired trafficking or instability of the mutant protein, as well as compromised intercellular communication is probably a concurrent result of the mutation. The results expand the genetic and phenotypic spectra of MIP and help to better understand the molecular basis of congenital cataracts.

show abstract

A 76-bp Deletion in the Mip Gene Causes Autosomal Dominant Cataract in Hfi Mice

Cited by 38 publications

References 27 publications

Characterization of a Mutation in the Lens-specific MP70 Encoding Gene of the Mouse Leading to a Dominant Cataract

Characterization of a Mutation in the Lens-specific MP70 Encoding Gene of the Mouse Leading to a Dominant Cataract

Structural Function of MIP/Aquaporin 0 in the Eye Lens; Genetic Defects Lead to Congenital Inherited Cataracts

A novel single‐base deletional mutation of MIP impairs protein distribution and cell‐to‐cell adhesion in autosomal dominant cataracts in a Chinese family

Contact Info

Product

Resources

About