This report describes spinocerebellar ataxia 13 (SCA13), which is a subtype of spinocerebellar ataxia; SCA13 is inherited as an autosomal dominant. The human gene implicated in this disease is KCNC3, which encodes the voltage-gated potassium channel, Shaw-related subfamily, member-3. There are two high-scoring fly orthologs, Shaw and Shawl, for which multiple genetic reagents have been generated, including classical amorphic alleles, RNAi targeting constructs, alleles caused by insertional mutagenesis, and targeted CRISPR knockout constructs.
Multiple UAS constructs of the human gene Hsap\KCNC3 have been introduced into flies, including wild-type KCNC3, and genes carrying a mutational lesions implicated in SCA13. See the 'Disease-Implicated Variants' table below. For an Hsap\KCNC3 gene carrying an implicated pathological lesion, expression in the developing eye results in mild phenotypes, including aberrant differentiation and polarity of photoreceptor cells.
For both Shaw and Shawl, pan-neuronal knockdown of expression effected by RNAi fails to induce any lethal, sterile, or visible phenotypes. Overexpression of Shaw results in multiple phenotypes, including lethality, depending upon the tissue and stage specificity of the driver used.
[updated Aug. 2021 by FlyBase; FBrf0222196]
The autosomal dominant cerebellar degenerative disorders are generally referred to as 'spinocerebellar ataxias,' (SCAs) even though 'spinocerebellar' is a hybrid term, referring to both clinical signs and neuroanatomical regions (Margolis, 2003, pubmed:14628900). Neuropathologists have defined SCAs as cerebellar ataxias with variable involvement of the brainstem and spinal cord, and the clinical features of the disorders are caused by degeneration of the cerebellum and its afferent and efferent connections, which involve the brainstem and spinal cord (Schols et al., 2004 pubmed:15099544; Taroni and DiDonato, 2004, pubmed:15263894). [From MIM:164400, 2015.10.27]
The autosomal dominant cerebellar degenerative disorders are generally referred to as 'spinocerebellar ataxias' (SCAs). Neuropathologists have defined SCAs as cerebellar ataxias with variable involvement of the brainstem and spinal cord; the clinical features of the disorders are caused by degeneration of the cerebellum and its afferent and efferent connections, which involve the brainstem and spinal cord (Schols et al., 2004 pubmed:15099544; Taroni and DiDonato, 2004, pubmed:15263894). [From MIM:164400, 2015.10.27]
[SPINOCEREBELLAR ATAXIA 13; SCA13](https://omim.org/entry/605259)
[POTASSIUM CHANNEL, VOLTAGE-GATED, SHAW-RELATED SUBFAMILY, MEMBER 3; KCNC3](https://omim.org/entry/176264)
In the families described to date, the phenotype of spinocerebellar ataxia type 13 (SCA13) has ranged from slowly progressive childhood-onset cerebellar gait ataxia associated with cerebellar dysarthria and often accompanied by mild intellectual disability and occasional seizures to adult-onset progressive ataxia. Life span is not shortened and many persons live beyond age 70 years, but assistance with gait may be required as the disease progresses. [From GeneReviews, Spinocerebellar Ataxia Type 13, pubmed:20301404, 2015.12.14]
This form of autosomal dominant spinocerebellar ataxia, SCA13, is caused by heterozygous mutation in KCNC3, the gene encoding the voltage-gated potassium channel, Shaw-related subfamily, member-3 gene. [From MIM:605259, 2015.10.30]
The molecular mechanisms responsible for generating diverse voltage-gated potassium channels were initially studied in Drosophila by cloning and sequencing the Shaker gene. Subsequently, 3 additional Drosophila genes, Shaw, Shab, and Shal, which share sequence relatedness to the Shaker gene, were isolated. This extended gene family in Drosophila is, at least in part, responsible for generating the diversity of potassium channels observed by physiologic techniques such as patch-clamping. Each member of the extended Drosophila gene family, Shaker, Shab, Shal, and Shaw, is represented by a mammalian homolog (Ghanshani et al., 1992, pubmed:1740329). [From MIM:176264, 2015.12.14]
Many to many (4 human to 2 Drosophila) (See DIOPT, link below).
