title: Feline hypersomatotropism and acromegaly tumorigenesis: a potential role for the AIP gene.
abstract: Acromegaly in humans is usually sporadic, however up to 20% of familial isolated pituitary adenomas are caused by germline sequence variants of the aryl-hydrocarbon-receptor interacting protein (AIP) gene. Feline acromegaly has similarities to human acromegalic families with AIP mutations. The aim of this study was to sequence the feline AIP gene, identify sequence variants and compare the AIP gene sequence between feline acromegalic and control cats, and in acromegalic siblings. The feline AIP gene was amplified through PCR using whole blood genomic DNA from 10 acromegalic and 10 control cats, and 3 sibling pairs affected by acromegaly. PCR products were sequenced and compared with the published predicted feline AIP gene. A single nonsynonymous SNP was identified in exon 1 (AIP:c.9T > G) of two acromegalic cats and none of the control cats, as well as both members of one sibling pair. The region of this SNP is considered essential for the interaction of the AIP protein with its receptor. This sequence variant has not previously been reported in humans. Two additional synonymous sequence variants were identified (AIP:c.481C > T and AIP:c.826C > T). This is the first molecular study to investigate a potential genetic cause of feline acromegaly and identified a nonsynonymous AIP single nucleotide polymorphism in 20% of the acromegalic cat population evaluated, as well as in one of the sibling pairs evaluated.
authors.affiliation: Clinical Science and Services, Royal Veterinary College, Hawkshead Lane, North Mymms, Hertfordshire AL9 7TA, UK. Electronic address: cscudder@rvc.ac.uk.
authors.forename: C J
authors.initials: CJ
authors.lastname: Scudder
authors.affiliation: Clinical Science and Services, Royal Veterinary College, Hawkshead Lane, North Mymms, Hertfordshire AL9 7TA, UK.
authors.forename: S J
authors.initials: SJ
authors.lastname: Niessen
authors.affiliation: Department of Pathology and Pathogen Biology, Hawkshead Lane, North Mymms, Hertfordshire AL9 7TA, UK.
authors.forename: B
authors.initials: B
authors.lastname: Catchpole
authors.affiliation: Department of Comparative and Biomedical Sciences, Royal Veterinary College, Royal College Street, London NW1 0TU, UK.
authors.forename: R C
authors.initials: RC
authors.lastname: Fowkes
authors.affiliation: Clinical Science and Services, Royal Veterinary College, Hawkshead Lane, North Mymms, Hertfordshire AL9 7TA, UK.
authors.forename: D B
authors.initials: DB
authors.lastname: Church
authors.affiliation: Clinical Science and Services, Royal Veterinary College, Hawkshead Lane, North Mymms, Hertfordshire AL9 7TA, UK.
authors.forename: Y
authors.initials: Y
authors.lastname: Forcada
mesh_terms: D000172:Acromegaly / Q000473:pathology / Q000662:veterinary*; D000375:Aging; D000595:Amino Acid Sequence; D000818:Animals; D063646:Carcinogenesis / Q000473:pathology*; D016022:Case-Control Studies; D002371:Cat Diseases / Q000235:genetics* / Q000473:pathology; D002415:Cats; D005260:Female; D020022:Genetic Predisposition to Disease; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D020641:Polymorphism, Single Nucleotide
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C103265:aryl hydrocarbon receptor-interacting protein
keywords: AIP; Acromegaly; Feline; Genetic; Hypersomatotropism; SNP