An Allele-Specific Genotyping Method for Rat Lyst (Lysosomal Trafficking Regulator) Gene

Masui, Norio; Mori, Masayuki; Nishikawa, Tetsu; Takagi, Yoshiomi; Asai, Hidekazu; Yanabe, Makoto; Yamasaki, Kenichi; Serikawa, Tadao; Sato, Katsunori

doi:10.1538/expanim.53.77

Cited by 3 publications

(3 citation statements)

References 13 publications

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“…The rat Foxn1 rnu gene was subjected to PCR-RFLP analysis using the restriction endonuclease, Tsp45I, as reported by Hirasawa et al [14]. The rat Lyst bg gene was diagnosed with longnested PCR analysis by two pairs of primers named Bg39A4//Bg52A4 and Bg39A4nes//Bg52A4nes which we designed in a previous study [18]. The first round of long-PCR amplification by the Bg39A4//Bg52A4 outer primer pair was carried out with initial incubation at 94°C for 1 min, followed by 25 cycles of denaturation at 94°C for 30 s, annealing and extension at 68°C for 20 min with a final extension at 72°C for 10 min.…”

Section: Molecular Genetic Diagnoses For the Disease Genesmentioning

confidence: 99%

“…It was estimated that a cross-intercross method would be less advantageous for establishing new beigenude rat strains. Recently, the molecular genetic diagnoses for both the Foxn1 rnu and Lyst bg genes have been developed [14,18] and they have enabled discrimination between the heterozygous mutants and the wild-type strain that could not be discriminated by appearance. Namely, both mutant genes can be heterozygously maintained in alternation of generations with no intercross and only continuous backcross.…”

Section: Introductionmentioning

confidence: 99%

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Establishment of a Set of Combined Immunodeficient DA/Slc-Foxn1rnu Lystbg Congenic Rat Strains

Masui¹,

Nishikawa

Takagi³

et al. 2004

Exp. Anim.

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Abstract:The congenitally athymic nude rat is used for studying cancer and transplantation owing to its hairlessness and T-cell defective function caused by the Foxn1 rnu gene. However, NK cell activity of the nude rat is markedly increased. It is known that NK cells play a major role in rejection of xenografts and in cytotoxicity against tumor cells. Thus, the athymic nude rat with impaired NK cell activity should be a useful model for extensive studies. The DA-Lyst bg /Lyst bg rat, a model for human Chediak-Higashi syndrome (CHS) is characterized by diluted-coat color and impairment of NK cell activity. We planned to establish a combined immunodeficient double mutant rat introgressed with the Foxn1 rnu and Lyst bg genes and a set of congenic strains having an identical genetic backgrounds simultaneously. Based on the phenotypic and genetic characteristics of the parental rat strains, the new strains were produced using continuous backcross and diagnosis with molecular genetic techniques. Each disease gene was diagnosed with PCR-RFLP or the long-nested PCR method. Furthermore, we used a marker-assisted congenic strategy based on scanning the genetic backgrounds of the parental rats with 461 rat microsatellite markers. We think that the newly established DA/Slc-Foxn1 rnu /Foxn1 rnu Lyst bg /Lyst bg double mutant will be useful as a severe disease model for human CHS, and the set of DA/SlcFoxn1 rnu Lyst bg congenic strains which have impaired NK cell activity and/or defective T cell function should be useful for studying in cancer research, xenotransplantation, immune function and other wide-ranging studies.

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Section: Molecular Genetic Diagnoses For the Disease Genesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Establishment of a Set of Combined Immunodeficient DA/Slc-Foxn1rnu Lystbg Congenic Rat Strains

Masui¹,

Nishikawa

Takagi³

et al. 2004

Exp. Anim.

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“…consistently identified within LYST. These species include, human [39][40][41][42] , cow 43 , mouse 44,45 , rat 46,47 and Aleutian mink 48 . Overall, in the public archive of human genetic variation and phenotypes (clinVar) 49 , over 40 different pathogenic variants have been identified in LYST in humans, including nonsense and missense mutations, as well as insertions and deletions.…”

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confidence: 99%

Assisted reproduction mediated resurrection of a feline model for Chediak-Higashi syndrome caused by a large duplication in LYST

Buckley

Grahn

Gandolfi

et al. 2020

Sci Rep

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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. Chediak-Higashi syndrome (CHS) (OMIM Accession: 214500) is a rare autosomal recessive disorder characterized in humans by severe immune deficiency, oculocutaneous albinism, bleeding tendencies, recurrent pyogenic infections, progressive neurologic defects and a lymphoproliferative syndrome. The most common cause of death from CHS is from recurrent infections or the development of an accelerated phase with hemophagocytic lymphohistiocytosis. Approximately 90% of deaths occur in the first decade of life, and those who survive into adulthood develop progressive neurological symptoms 1. The disease was first described in the 1940s to early 1950s 2-6 and has been characterized in a host of diverse species, including cow 7-10 , mink 10-14 , killer whale 15,16 , fox 17,18 and domestic cat 19-23 (OMIA: 000185-9913, 9733, 494514, 452646, 9685). Continuing studies of CHS models have demonstrated their value in deciphering delta storage pool deficiencies 24 , heritable platelet disorders 25,26 and cellular cytotoxicity 27. Bone marrow transplantation has been a viable option for management of human CHS for over 30 years 28-31. The genetic cause for CHS was first defined in rodents 32-36 , with the locus historically known as beige due to the associated hypopigmentation phenotype 33. The human homolog of the mouse beige locus revealed the first causative mutations for CHS in humans 37,38 and was defined as lysosomal trafficking regulator (LYST) 37. In humans, LYST encodes a 3,801 amino acid protein (11.4 kb transcript), which regulates intracellular protein trafficking to and from the lysosome (GCID:GC01M235824). In many species with CHS, mutations have been

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Chediak-Higashi syndrome

Kaplan

Domenico

Ward

2008

Current Opinion in Hematology

317

263

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An Allele-Specific Genotyping Method for Rat Lyst (Lysosomal Trafficking Regulator) Gene

Cited by 3 publications

References 13 publications

Establishment of a Set of Combined Immunodeficient DA/Slc-Foxn1rnu Lystbg Congenic Rat Strains

Establishment of a Set of Combined Immunodeficient DA/Slc-Foxn1rnu Lystbg Congenic Rat Strains

Assisted reproduction mediated resurrection of a feline model for Chediak-Higashi syndrome caused by a large duplication in LYST

Chediak-Higashi syndrome

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