This report describes neuronal ceroid lipofuscinosis 3 (NCL3), which is a subtype of neuronal ceroid lipofuscinosis; NCL3 exhibits autosomal recessive inheritance. NCL3 is also called juvenile neuronal ceroid lipofuscinosis (JNCL) or Batten disease. The human gene implicated in this disease is CLN3, which affects palmitoyl-protein desaturation and plays a role in membrane-associated proteolipid modification. There is a single fly ortholog, Dmel\Cln3, for which an amorphic allele, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated.
Several UAS constructs of the human Hsap\CLN3 gene have been introduced into flies, including wild-type CLN3. Ubiquitous overexpression is semi-lethal; expression in various tissues results in visible phenotypes in the adult.
Animals homozygous for an amorphic mutation of Dmel\Cln3 are viable and fertile; they exhibit hypersensitivity to oxidative stress. Using UAS constructs of Dmel\Cln3, overexpression in the eye results in a rough, glazed eye phenotype; assays using this and other overexpression phenotypes have allowed characterization of genetic interactions, see the Cln3 gene report.
A YFP-fusion construct has allowed visualization of protein distribution. In Drosophila, this protein has restricted expression: it is detected in the larval CNS, predominantly in the glia that form the insect blood-brain-barrier; it is also strongly expressed in Malpighian tubules.
[updated Apr. 2017 by FlyBase; FBrf0222196]
The neuronal ceroid lipofuscinoses (NCLs or CLNs) are a clinically heterogeneous group of neurodegenerative disorders; the general clinical course includes progressive dementia, seizures, and progressive visual failure (Mole et al., 2005; pubmed:15965709). [from MIM:256730; 2016.01.05]
Individuals with all forms NCL have shortened life expectancy, but it is highly variable, depending upon the form of the disease (from Medscape, http://emedicine.medscape.com/article/1178391-overview; 2016.01.05).
The term Batten disease may refer specifically to the juvenile-onset form, but is also used to refer to any NCL.
[CEROID LIPOFUSCINOSIS, NEURONAL, 3; CLN3](https://omim.org/entry/204200)
[CLN3 LYSOSOMAL/ENDOSOMAL TRANSMEMBRANE PROTEIN, BATTENIN; CLN3](https://omim.org/entry/607042)
After a few years of normal development, children with juvenile-onset NCL develop progressive vision loss, intellectual and motor disability, speech difficulties, and seizures. Vision impairment is often the first noticeable sign of the disease, beginning between the ages of 4 and 8 years; most individuals survive to their twenties or thirties. [Genetics Home Reference: Juvenile Batten disease; 2016.01.05]
See general description of neuronal ceroid lipofuscinosis, above. CLN3 is most commonly a juvenile-onset form of the disease. [from MIM:204200; 2016.01.05]
Neuronal ceroid lipofuscinosis 3 (CLN3) is inherited as an autosomal recessive and is caused by homozygous or compound heterozygous mutation in the CLN3 gene.
The hallmark of CLN3 is the ultrastructural pattern of lipopigment with a 'fingerprint' profile, which can have 3 different appearances: pure within a lysosomal residual body; in conjunction with curvilinear or rectilinear profiles; and as a small component within large membrane-bound lysosomal vacuoles. The combination of fingerprint profiles within lysosomal vacuoles is a regular feature of blood lymphocytes from patients with CLN3 (Mole et al., 2005; pubmed:15965709). [from MIM:204200; 2016.01.05]
The CLN3 protein effects palmitoyl-protein desaturation and plays a role in membrane-associated proteolipid modification (Narayan et al., 2006; pubmed:17036287). [from MIM:204200; 2016.01.05] Palmitoylation functions as a reversible posttranslational modification to target signaling molecules to specialized membrane domains (Narayan et al., 2006; pubmed:17036287).
One to one: 1 human to 1 Drosophila (reciprocal best hit).
High-scoring ortholog of human CLN3 (1 Drosophila to 1 human). Dmel\cln3 shares 42% identity and 62% similarity with human CLN3.
