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Cloning and characterization of the mouse Mcoln1 gene reveals an alternatively spliced transcript not seen in humans.

Falardeau JL, Kennedy JC, Acierno JS, Sun M, Stahl S, Goldin E, Slaugenhaupt SA - BMC Genomics (2002)

Bottom Line: The transcript that results from murine specific alternative splicing encodes a 611 amino acid protein that differs at the c-terminus.Mcoln1 is highly similar to MCOLN1, especially in the transmembrane domains and ion pore region.To date, there are very few reports describing species-specific splice variants.

View Article: PubMed Central - HTML - PubMed

Affiliation: Harvard Institute of Human Genetics, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA. falardea@helix.mgh.harvard.edu

ABSTRACT

Background: Mucolipidosis type IV (MLIV) is an autosomal recessive lysosomal storage disorder characterized by severe neurologic and ophthalmologic abnormalities. Recently the MLIV gene, MCOLN1, has been identified as a new member of the transient receptor potential (TRP) cation channel superfamily. Here we report the cloning and characterization of the mouse homologue, Mcoln1, and report a novel splice variant that is not seen in humans.

Results: The human and mouse genes display a high degree of synteny. Mcoln1 shows 91% amino acid and 86% nucleotide identity to MCOLN1. Also, Mcoln1 maps to chromosome 8 and contains an open reading frame of 580 amino acids, with a transcript length of approximately 2 kb encoded by 14 exons, similar to its human counterpart. The transcript that results from murine specific alternative splicing encodes a 611 amino acid protein that differs at the c-terminus.

Conclusions: Mcoln1 is highly similar to MCOLN1, especially in the transmembrane domains and ion pore region. Also, the late endosomal/lysosomal targeting signal is conserved, supporting the hypothesis that the protein is localized to these vesicle membranes. To date, there are very few reports describing species-specific splice variants. While identification of Mcoln1 is crucial to the development of mouse models for MLIV, the fact that there are two transcripts in mice suggests an additional or alternate function of the gene that may complicate phenotypic assessment.

No MeSH data available.


Related in: MedlinePlus

Peptide sequence comparison of Mcoln1 to human, D. melanogaster, and C. elegans (cup-5) homologues. Blue lines indicate transmembrane domains, the red box surrounds the putative channel pore, the orange box surrounds the putative late endosomal/lysosomal targeting signal.
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Figure 2: Peptide sequence comparison of Mcoln1 to human, D. melanogaster, and C. elegans (cup-5) homologues. Blue lines indicate transmembrane domains, the red box surrounds the putative channel pore, the orange box surrounds the putative late endosomal/lysosomal targeting signal.

Mentions: Comparison of the mouse and human peptide sequences showed 91% identity (Fig. 2). The C. elegans homologue cup-5 shows 34% identity with Mcoln1 and BLASTP analysis of Mcoln1 identified a putative Drosophila melanogaster homologue that shows 38% identity (Fig. 2). Interestingly, two MCOLN1 amino acid substitutions that result in MLIV occur at conserved amino acids. TMPred analysis predicts a protein structure that is nearly identical to MCOLN1, containing 6 transmembrane domains with the N- and C-termini residing in the cytoplasm (Fig. 2) [9].


Cloning and characterization of the mouse Mcoln1 gene reveals an alternatively spliced transcript not seen in humans.

Falardeau JL, Kennedy JC, Acierno JS, Sun M, Stahl S, Goldin E, Slaugenhaupt SA - BMC Genomics (2002)

Peptide sequence comparison of Mcoln1 to human, D. melanogaster, and C. elegans (cup-5) homologues. Blue lines indicate transmembrane domains, the red box surrounds the putative channel pore, the orange box surrounds the putative late endosomal/lysosomal targeting signal.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC88885&req=5

Figure 2: Peptide sequence comparison of Mcoln1 to human, D. melanogaster, and C. elegans (cup-5) homologues. Blue lines indicate transmembrane domains, the red box surrounds the putative channel pore, the orange box surrounds the putative late endosomal/lysosomal targeting signal.
Mentions: Comparison of the mouse and human peptide sequences showed 91% identity (Fig. 2). The C. elegans homologue cup-5 shows 34% identity with Mcoln1 and BLASTP analysis of Mcoln1 identified a putative Drosophila melanogaster homologue that shows 38% identity (Fig. 2). Interestingly, two MCOLN1 amino acid substitutions that result in MLIV occur at conserved amino acids. TMPred analysis predicts a protein structure that is nearly identical to MCOLN1, containing 6 transmembrane domains with the N- and C-termini residing in the cytoplasm (Fig. 2) [9].

Bottom Line: The transcript that results from murine specific alternative splicing encodes a 611 amino acid protein that differs at the c-terminus.Mcoln1 is highly similar to MCOLN1, especially in the transmembrane domains and ion pore region.To date, there are very few reports describing species-specific splice variants.

View Article: PubMed Central - HTML - PubMed

Affiliation: Harvard Institute of Human Genetics, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA. falardea@helix.mgh.harvard.edu

ABSTRACT

Background: Mucolipidosis type IV (MLIV) is an autosomal recessive lysosomal storage disorder characterized by severe neurologic and ophthalmologic abnormalities. Recently the MLIV gene, MCOLN1, has been identified as a new member of the transient receptor potential (TRP) cation channel superfamily. Here we report the cloning and characterization of the mouse homologue, Mcoln1, and report a novel splice variant that is not seen in humans.

Results: The human and mouse genes display a high degree of synteny. Mcoln1 shows 91% amino acid and 86% nucleotide identity to MCOLN1. Also, Mcoln1 maps to chromosome 8 and contains an open reading frame of 580 amino acids, with a transcript length of approximately 2 kb encoded by 14 exons, similar to its human counterpart. The transcript that results from murine specific alternative splicing encodes a 611 amino acid protein that differs at the c-terminus.

Conclusions: Mcoln1 is highly similar to MCOLN1, especially in the transmembrane domains and ion pore region. Also, the late endosomal/lysosomal targeting signal is conserved, supporting the hypothesis that the protein is localized to these vesicle membranes. To date, there are very few reports describing species-specific splice variants. While identification of Mcoln1 is crucial to the development of mouse models for MLIV, the fact that there are two transcripts in mice suggests an additional or alternate function of the gene that may complicate phenotypic assessment.

No MeSH data available.


Related in: MedlinePlus