Intermediate levels of neuronal palmitoyl-protein Delta-9 desaturase in heterozygotes for murine Batten disease.
We recently demonstrated reduced activity of a novel palmitoyl-protein Delta-9 desaturase in neuronal tissues from mice with the cln3 Juvenile Neuronal Ceroid-Lipofuscinosis (Batten disease) gene ablated. In this follow-up study we have been able to obtain tissues from heterozygous cln3 mice and report that the enzyme activity in brain and pancreas from the heterozygotes is intermediate at 40% of the wild-type activity and consistent with recessive inheritance. Neuronal tissues from the CLN1 knock-out mouse demonstrated normal enzymatic activity pointing to the specificity of the desaturase function to CLN3. Non-neuronal tissues did not have measurable desaturase activity in wild-type or knock-out mice using this assay system. This may be due to lack of sensitivity of our assay system in these tissues or failure to activate the enzyme in these tissues. This is the first report of a heterozygous abnormality in Batten disease and provides important confirmation that this is the function of the CLN3 protein in neuronal tissues.
Narayan
Srinivas B
SB
Department of Pathology and Laboratory Medicine, The Children's Hospital of Philadelphia, 34th Street & Civic Center Boulevard, Philadelphia, PA 19104, USA. Narayans@email.chop.edu
Tan
Lu
L
Bennett
Michael J
MJ
D000818:Animals; D001921:Brain / Q000201:enzymology; D006579:Heterozygote; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008818:Mice, Neurologic Mutants; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism*; D009472:Neuronal Ceroid-Lipofuscinoses / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*; D009474:Neurons / Q000201:enzymology* / Q000473:pathology; D010179:Pancreas / Q000201:enzymology; D013869:Thiolester Hydrolases / Q000235:genetics / Q000378:metabolism
C102229:CLN3 protein, mouse; D008562:Membrane Glycoproteins; D018832:Molecular Chaperones; D013869:Thiolester Hydrolases; C095299:palmitoyl-protein thioesterase