Assisted reproduction mediated resurrection of a feline model for Chediak-Higashi syndrome caused by a large duplication in LYST
| Autor: | Reuben M. Buckley, Mark D Kittleson, Robert A. Grahn, Jason R. Herrick, H. L. Bateman, William F. Swanson, J. Newsom, Leslie A. Lyons, D. J. Prieur, Barbara Gandolfi |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Male Gene duplication Genotype Vesicular Transport Proteins lcsh:Medicine 030204 cardiovascular system & hematology Biology medicine.disease_cause Article Cell Line 03 medical and health sciences 0302 clinical medicine Genetic hemic and lymphatic diseases Lysosomal trafficking regulator Genetics medicine 2.1 Biological and endogenous factors Animals Aetiology Allele Polymorphism lcsh:Science Genotyping Alleles Animal breeding Mutation Polymorphism Genetic Multidisciplinary Animal Chédiak–Higashi syndrome lcsh:R Exons Fibroblasts medicine.disease Pedigree Disease Models Animal 030104 developmental biology Disease Models Cats lcsh:Q Female Tandem exon duplication Chediak-Higashi Syndrome Medical genomics |
| Zdroj: | Scientific reports, vol 10, iss 1 Scientific Reports, Vol 10, Iss 1, Pp 1-9 (2020) Scientific Reports |
| Popis: | Chediak-Higashi Syndrome (CHS) is a well-characterized, autosomal recessively inherited lysosomal disease caused by mutations in lysosomal trafficking regulator (LYST). The feline model for CHS was originally maintained for ~20 years. However, the colonies were disbanded and the CHS cat model was lost to the research community before the causative mutation was identified. To resurrect the cat model, semen was collected and cryopreserved from a lone, fertile, CHS carrier male. Using cryopreserved semen, laparoscopic oviductal artificial insemination was performed on three queens, two queens produced 11 viable kittens. To identify the causative mutation, a fibroblast cell line, derived from an affected cat from the original colony, was whole genome sequenced. Visual inspection of the sequence data identified a candidate causal variant as a ~20 kb tandem duplication within LYST, spanning exons 30 through to 38 (NM_001290242.1:c.8347-2422_9548 + 1749dup). PCR genotyping of the produced offspring demonstrated three individuals inherited the mutant allele from the CHS carrier male. This study demonstrated the successful use of cryopreservation and assisted reproduction to maintain and resurrect biomedical models and has defined the variant causing Chediak-Higashi syndrome in the domestic cat. |
| Databáze: | OpenAIRE |
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