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Assisted reproduction mediated resurrection of a feline model for Chediak-Higashi syndrome caused by a large duplication in LYST
- Source :
- Scientific reports, vol 10, iss 1, Scientific Reports, Vol 10, Iss 1, Pp 1-9 (2020), Scientific Reports
- Publication Year :
- 2020
- Publisher :
- eScholarship, University of California, 2020.
-
Abstract
- 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.
- Subjects :
- 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
Subjects
Details
- Database :
- OpenAIRE
- Journal :
- Scientific reports, vol 10, iss 1, Scientific Reports, Vol 10, Iss 1, Pp 1-9 (2020), Scientific Reports
- Accession number :
- edsair.doi.dedup.....0256c7bb7bbb91969681497ce8f80958