Mcoln1-/- mice may be useful for studying the lysosomal storage disorder Mucolipidosis type IV (MLIV).
Susan Slaugenhaupt, Harvard Medical School
Mcoln1-/- mice contain a neo cassette replacing exons 3-4 and part of exon 5 of the mucolipin 1 (Mcoln1) gene, abolishing gene expression. Mcoln1 encodes a transmembrane cation channel localized to intracellular vesicular membranes including lysosomes, and functions in the late endocytic pathway and in the regulation of lysosomal exocytosis. Mutations in MCOLN1 have been associated with Mucolipidosis type IV (MLIV), an autosomal recessive lysosomal storage disorder characterized by severe mental retardation, delayed motor milestones, ophthalmologic abnormalities, constitutive achlorhydria, and elevated plasma gastrin levels. Homozygotes are viable and fertile with a median age of 8 months. Mice exhibit numerous dense inclusion bodies in all cell types in brain, elevated plasma gastrin, vacuolization in parietal cells, and retinal degeneration. They have neurological defects as evident by gait deficits at 6.5 months of age, leading to complete hind-limb paralysis in 3-4 weeks. They also exhibit limb clasping at 3 months, loss of subcutaneous fat, and decreased muscle mass at the end-stage.
A targeting vector was designed to replace exons 3-4 and part of exon 5 encoding the mucolipin 1 (Mcoln1) gene with a neomycin resistance (neo) cassette in reverse orientation to the gene. The construct was electroporated into (C57BL/6 x 129S6/SvEvTac)F1-derived LC3 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts and the resulting chimeric males were bred to C57BL/6J females. Mcoln1-/- mice were backcrossed to C57BL/6J mice for at least 15 generations. Upon arrival at The Jackson Laboratory, mice were bred to C57BL/6J (Stock No. 000664) for at least one generation to establish the colony.
|Allele Name||targeted mutation 1, Susan A Slaugenhaupt|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Mcoln1, mucolipin 1|
|Strain of Origin||(C57BL/6N x 129S6/SvEvTac)F1|
|General Note||ES cell line = LC3, which carries GFP.|
|Molecular Note||Exons 3, 4 and part of exon 5 were replaced with a neo cassette. The absence of transcript was confirmed by RT-PCR on brain extracts.|
When maintaining a live colony, heterozygous mice may be bred to wildtype mice from the colony. Homozygous mice develop hind-limb paralysis by 6.5 months of age and have an average life expectancy of 8 months.
When using the Mcoln1- mouse strain in a publication, please cite the originating article(s) and include JAX stock #027110 in your Materials and Methods section.