Molecular cloning and characterization of the family of feline leucine-rich glioma-inactivated (LGI) genes, and mutational analysis in familial spontaneous epileptic cats
Abstract Background 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. Familial sponta...
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| Format: | Article |
| Language: | English |
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BMC
2017-12-01
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| Series: | BMC Veterinary Research |
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| Online Access: | http://link.springer.com/article/10.1186/s12917-017-1308-9 |
| _version_ | 1828869494500491264 |
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| author | Yoshihiko Yu Daisuke Hasegawa Aki Fujiwara-Igarashi Yuji Hamamoto Shunta Mizoguchi Takayuki Kuwabara Michio Fujita |
| author_facet | Yoshihiko Yu Daisuke Hasegawa Aki Fujiwara-Igarashi Yuji Hamamoto Shunta Mizoguchi Takayuki Kuwabara Michio Fujita |
| author_sort | Yoshihiko Yu |
| collection | DOAJ |
| description | Abstract Background 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. 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. Results The 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. Conclusions We 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. |
| first_indexed | 2024-12-13T05:51:39Z |
| format | Article |
| id | doaj.art-338aae933ae848c6b84484de876457b5 |
| institution | Directory Open Access Journal |
| issn | 1746-6148 |
| language | English |
| last_indexed | 2024-12-13T05:51:39Z |
| publishDate | 2017-12-01 |
| publisher | BMC |
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| series | BMC Veterinary Research |
| spelling | doaj.art-338aae933ae848c6b84484de876457b52022-12-21T23:57:32ZengBMCBMC Veterinary Research1746-61482017-12-0113111310.1186/s12917-017-1308-9Molecular cloning and characterization of the family of feline leucine-rich glioma-inactivated (LGI) genes, and mutational analysis in familial spontaneous epileptic catsYoshihiko Yu0Daisuke Hasegawa1Aki Fujiwara-Igarashi2Yuji Hamamoto3Shunta Mizoguchi4Takayuki Kuwabara5Michio Fujita6Department of Clinical Veterinary Medicine, Nippon Veterinary and Life Science UniversityDepartment of Clinical Veterinary Medicine, Nippon Veterinary and Life Science UniversityDepartment of Clinical Veterinary Medicine, Nippon Veterinary and Life Science UniversityDepartment of Clinical Veterinary Medicine, Nippon Veterinary and Life Science UniversityDepartment of Clinical Veterinary Medicine, Nippon Veterinary and Life Science UniversityDepartment of Clinical Veterinary Medicine, Nippon Veterinary and Life Science UniversityDepartment of Clinical Veterinary Medicine, Nippon Veterinary and Life Science UniversityAbstract Background 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. 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. Results The 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. Conclusions We 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.http://link.springer.com/article/10.1186/s12917-017-1308-9FelineEpilepsyLgiCloning and sequence analysisMolecular characterization |
| spellingShingle | Yoshihiko Yu Daisuke Hasegawa Aki Fujiwara-Igarashi Yuji Hamamoto Shunta Mizoguchi Takayuki Kuwabara Michio Fujita Molecular cloning and characterization of the family of feline leucine-rich glioma-inactivated (LGI) genes, and mutational analysis in familial spontaneous epileptic cats BMC Veterinary Research Feline Epilepsy Lgi Cloning and sequence analysis Molecular characterization |
| title | Molecular cloning and characterization of the family of feline leucine-rich glioma-inactivated (LGI) genes, and mutational analysis in familial spontaneous epileptic cats |
| title_full | Molecular cloning and characterization of the family of feline leucine-rich glioma-inactivated (LGI) genes, and mutational analysis in familial spontaneous epileptic cats |
| title_fullStr | Molecular cloning and characterization of the family of feline leucine-rich glioma-inactivated (LGI) genes, and mutational analysis in familial spontaneous epileptic cats |
| title_full_unstemmed | Molecular cloning and characterization of the family of feline leucine-rich glioma-inactivated (LGI) genes, and mutational analysis in familial spontaneous epileptic cats |
| title_short | Molecular cloning and characterization of the family of feline leucine-rich glioma-inactivated (LGI) genes, and mutational analysis in familial spontaneous epileptic cats |
| title_sort | molecular cloning and characterization of the family of feline leucine rich glioma inactivated lgi genes and mutational analysis in familial spontaneous epileptic cats |
| topic | Feline Epilepsy Lgi Cloning and sequence analysis Molecular characterization |
| url | http://link.springer.com/article/10.1186/s12917-017-1308-9 |
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