Congenital ovine neuronal ceroid lipofuscinosis--a cathepsin D deficiency with increased levels of the inactive enzyme.
We recently showed that a form of neuronal ceroid lipofuscinosis (NCL) in white Swedish landrace sheep is caused by a missense mutation in the cathepsin D gene resulting in complete inactivation of the enzyme. Despite the lack of cathepsin D activity, the brains of the cathepsin D deficient sheep showed strongly increased staining for cathepsin D in immunohistochemistry. By Western blotting, a 5-10 fold increase in the level of cathepsin D was confirmed. These results indicate that the missense mutation in congenital NCL sheep results in the synthesis of an inactive yet stable cathepsin D.
Tyynelä
J
J
Institute of Biomedicine, POB8, 00014 University of Helsinki, Finland. jaana.tyynela@helsinki.fi
Sohar
I
I
Sleat
D E
DE
Gin
R M
RM
Donnelly
R J
RJ
Baumann
M
M
Haltia
M
M
Lobel
P
P
D000818:Animals; D002402:Cathepsin D / Q000032:analysis / Q000172:deficiency* / Q000235:genetics; D005625:Frontal Lobe / Q000201:enzymology; D008247:Lysosomes / Q000201:enzymology; D020125:Mutation, Missense; D009410:Nerve Degeneration / Q000151:congenital / Q000201:enzymology; D009472:Neuronal Ceroid-Lipofuscinoses / Q000151:congenital / Q000201:enzymology*; D012756:Sheep
D002402:Cathepsin D