Abstract
BackgroundLeucine-rich glioma-inactivated (LGI) proteins play a critical role in synaptic transmission. Dysfunction of these genes and encoded proteins is associated with neurological disorders such as genetic epilepsy or autoimmune limbic encephalitis in animals and human. Familial spontaneous epileptic cats (FSECs) are the only feline strain and animal model of familial temporal lobe epilepsy. The seizure semiology of FSECs comprises recurrent limbic seizures with or without evolution into generalized epileptic seizures, while cats with antibodies against voltage-gated potassium channel complexed/LGI1 show limbic encephalitis and recurrent limbic seizures. However, it remains unclear whether the genetics underlying FSECs are associated with LGI family genes. In the present study, we cloned and characterized the feline LGI1–4 genes and examined their association with FSECs. Conventional PCR techniques were performed for cloning and mutational analysis. Characterization was predicted using bioinformatics software.ResultsThe cDNAs of feline LGI1–4 contained 1674-bp, 1650-bp, 1647-bp, and 1617-bp open reading frames, respectively, and encoded proteins comprising 557, 549, 548, and 538 amino acid residues, respectively. The feline LGI1–4 putative protein sequences showed high homology with Homo sapiens, Canis familiaris, Bos taurus, Sus scrofa, and Equus caballus (92%–100%). Mutational analysis in 8 FSECs and 8 controls for LGI family genes revealed 3 non-synonymous and 14 synonymous single nucleotide polymorphisms in the coding region. Only one non-synonymous single nucleotide polymorphism in LGI4 was found in 3 out of 8 FSECs. Using three separate computational tools, this mutation was not predicted to be disease causing. No co-segregation of the disease was found with any variant.ConclusionsWe cloned the cDNAs of the four feline LGI genes, analyzed the amino acid sequences, and revealed that epilepsy in FSEC is not a monogenic disorder associated with LGI genes.
Highlights
Leucine-rich glioma-inactivated (LGI) proteins play a critical role in synaptic transmission
Vestibular stimulation-induced generalized epileptic seizures is the other seizure type in Familial spontaneous epileptic cats (FSEC), and is similar to the widely used EL mouse model, which shows genetic epilepsy [12]. As both the kindling/kainate model and the EL mouse are used to model human mesial temporal lobe epilepsy (MTLE), we consider that FSECs are a natural genetic model of human and feline Temporal lobe epilepsy (TLE)
Characterization of full-length feline LGI DNA complementary to RNA (cDNA) We cloned and sequenced the fLGI1, fLGI2, fLGI3, and fLGI4 cDNAs, and sequences were submitted to the DNA Databank of Japan under accession numbers LC309277, LC309278, LC309279, and LC309280, respectively
Summary
Leucine-rich glioma-inactivated (LGI) proteins play a critical role in synaptic transmission Dysfunction of these genes and encoded proteins is associated with neurological disorders such as genetic epilepsy or autoimmune limbic encephalitis in animals and human. The seizure semiology of FSECs comprises recurrent limbic seizures with or without evolution into generalized epileptic seizures, while cats with antibodies against voltage-gated potassium channel complexed/LGI1 show limbic encephalitis and recurrent limbic seizures It remains unclear whether the genetics underlying FSECs are associated with LGI family genes. Vestibular stimulation-induced generalized epileptic seizures is the other seizure type in FSECs, and is similar to the widely used EL mouse model, which shows genetic epilepsy [12] As both the kindling/kainate model and the EL mouse are used to model human mesial temporal lobe epilepsy (MTLE), we consider that FSECs are a natural genetic model of human and feline TLE. As such, understanding the genetic causes of FSECs may be useful in exploring the genetics of familial epilepsy
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
