title: Furosemide loading test in a case of homozygous solute carrier family 12, member 1 (SLC12A1) mutation (g.62382825G>A, p.Pro372Leu) in Japanese Black cattle.
abstract: Hydrallantois is the excessive accumulation of fluid in the allantoic cavity in a pregnant animal and is associated with fetal death. We recently identified a recessive missense mutation in the solute carrier family 12, member 1 (SLC12A1) gene (g.62382825G>A, p.Pro372Leu) that is associated with hydrallantois in Japanese Black cattle. Unexpectedly, we found a case of the homozygous risk-allele for SLC12A1 in a calf, using a PCR-based direct DNA sequencing test. The homozygote was outwardly healthy up to 3 months of age and the mother did not exhibit any clinical symptoms of hydrallantois. In order to validate these observations, we performed confirmation tests for the genotype and a diuretic loading test using furosemide, which inhibits the transporter activity of the SLC12A1 protein. The results showed that the calf was really homozygous for the risk-allele. In the homozygous calf, administration of furosemide did not alter urinary Na+or Cl-levels, in contrast to the heterozygote and wild-type calves in which these were significantly increased. These results demonstrate that the SLC12A1 (g.62382825G>A, p.Pro372Leu) is a hypomorphic or loss-of-function mutation and the hydrallantois with this mutation shows incomplete penetrance in Japanese Black cattle.
authors.affiliation: Shimane Prefecture Livestock Technology Center, Koshi, Izumo, Shimane, Japan.
authors.forename: Kiyotoshi
authors.initials: K
authors.lastname: Hasegawa
authors.affiliation: Shirakawa Institute of Animal Genetics, Japan Livestock Technology Association, Odakura, Nishigo, Fukushima, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Sasaki
authors.affiliation: Shimane Prefecture Livestock Technology Center, Koshi, Izumo, Shimane, Japan.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Sakamoto
authors.affiliation: Shimane Prefecture Livestock Technology Center, Koshi, Izumo, Shimane, Japan.
authors.forename: Akifumi
authors.initials: A
authors.lastname: Takano
authors.affiliation: Shimane Prefecture Livestock Technology Center, Koshi, Izumo, Shimane, Japan.
authors.forename: Megumi
authors.initials: M
authors.lastname: Takayama
authors.affiliation: Shimane Prefecture Livestock Division Livestock Hygiene Research Office, Jinzaioki, Izumo, Shimane, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Higashi
authors.affiliation: Shirakawa Institute of Animal Genetics, Japan Livestock Technology Association, Odakura, Nishigo, Fukushima, Japan.
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Sugimoto
authors.affiliation: Shimane Prefecture Livestock Technology Center, Koshi, Izumo, Shimane, Japan.
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Yasuda
mesh_terms: D000482:Allantois; D000483:Alleles; D000818:Animals; D002417:Cattle / Q000235:genetics*; D002418:Cattle Diseases / Q000235:genetics*; D004231:Diuresis / Q000187:drug effects / Q000235:genetics; D004487:Edema / Q000235:genetics* / Q000503:physiopathology / Q000662:veterinary*; D005260:Female; D005313:Fetal Death / Q000209:etiology; D005665:Furosemide / Q000494:pharmacology; D005808:Genes, Recessive / Q000235:genetics; D056726:Genetic Association Studies / Q000662:veterinary*; D006720:Homozygote; D020125:Mutation, Missense / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D011248:Pregnancy Complications / Q000235:genetics* / Q000662:veterinary*; D021381:Protein Transport / Q000187:drug effects; D012306:Risk; D017422:Sequence Analysis, DNA; D028021:Sodium-Potassium-Chloride Symporters / Q000235:genetics*; D064466:Solute Carrier Family 12, Member 1 / Q000235:genetics* / Q000378:metabolism
chemical_list: D028021:Sodium-Potassium-Chloride Symporters; D064466:Solute Carrier Family 12, Member 1; D005665:Furosemide
keywords: SLC12A1; autosomal recessive disorder; fetal mortality; hydrallantois (hydrops allantois); incomplete penetrance