Neuronal ceroid lipofuscinoses (NCLs, Batten disease) are group of inherited
childhood neurodegenerative diseases. Protein filled storage bodies accumulate in
neurons as well as in most other cells. This protein storage is specific. Subunit c of
mitochondrial ATP synthase accumulates in nearly all forms of the disease. Each
form is caused by mutations in a separate gene and there are at least 8 of these. It has
been proposed that these genes encode components of a specific pathway or
oligomeric complex for subunit c turnover.
NCLs also occur in animals, the best described being a form in New Zealand sheep
that are orthologous to the human CLN 6 late infantile variant disease. This
investigation was aimed at determining the sequence of the ovine gene for another
human form, CLN5, to allow studies of co-operativity and cross regulation between
these gene products.
Sequence of ovine CLN5 was found but it is most likely that the gene is differently
organised in sheep than in humans. PCR primers designed from the human gene
sequence amplified products from exons I and IV of human genomic DNA but only
from the region of the equivalent ex on N in sheep. A 125 bp oville fragment had
97% homology to part of human ex on IV. Primers degenerate at the 3' end were
tested to ensure that lack of ovine ex on I amplification was not due to specific
nucleotide differences at the polymerase start site. Different annealing temperatures
and magnesium concentrations were also tested. Primers to cDNA spaning exons 1-3
gave several PCR products, but the band of the predicted size contained cDNA of
which 55 bp were 88% homologous with a human type III inositol triphosphate
receptor, reading in the reverse direction on the complimentary strand.
The region for human CLN5, at 13q21, is gene rich and CLN5 is overlapped by at lest
2 other genes reading in the opposite direction, coding in both exons and introns of
CLN5. cDNA arising from splicing variants of the human CLN5 have also been
detected, but not fully characterised. The exon-intron boundary at the 3' end of ex on
I is read through by at least one of these. Full genomic sequencing of the region is
required to work out the structure of ovine CLN5.[Show full abstract]
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