El. Aronovich et al., Molecular basis of mucopolysaccharidosis type IIIB in emu (Dromaius novaehollandiae): An avian model of Sanfilippo syndrome type B, GENOMICS, 74(3), 2001, pp. 299-305
Sanfilippo syndrome type B, or mucopolysaccharidosis (MPS) IIIB, is an auto
somal recessive disease caused by a deficiency of lysosomal alpha -N-acetyl
glucosaminidase (NAC:LU). In Dromaius novaehollandiae (emu), a progressive
neurologic disease was recently discovered, which was characterized by NAGL
U deficiency and heparan sulfate accumulation. To define the molecular basi
s, the sequences of the normal emu NAGLU cDNA and gene were determined by P
CR-based approaches using primers for highly conserved regions of evolution
arily distant NAGLU homologues. It was observed that the emu NAGLU gene is
structurally similar to that of human and mouse, but the introns are consid
erably shorter. The cDNA had an open reading frame (ORF) of 2259 bp. The de
duced amino acid sequence is estimated to share 64% identity with human, 63
% with mouse, 41% with Drosophila, 39% with tobacco, and 35% with the Caeno
rhabditis elegans enzyme. Three normal and two affected emus were studied f
or nucleotide sequence covering the entire coding region and exon-intron bo
undaries. Unlike the human gene, emu NAG;LU appeared to be highly polymorph
ic: 19 variations were found in the coding region alone. The two affected e
mus were found to be homozygous for a 2-bp deletion, 1098-1099delGG, in exo
n 6. The resulting frameshift predicts a longer ORF of 2370 bp encoding a p
olypeptide with 37 additional amino acids and 387 altered amino acids. The
availability of mutation screening in emus now permits early detection of M
PS IIIB in breeding stocks and is an important step in characterizing this
unique, naturally occurring avian model for the development of gene transfe
r studies. (C) 2001 Academic Press.