title: Characterisation of a C1qtnf5 Ser163Arg knock-in mouse model of late-onset retinal macular degeneration.
abstract: A single founder mutation resulting in a Ser163Arg substitution in the C1QTNF5 gene product causes autosomal dominant late-onset retinal macular degeneration (L-ORMD) in humans, which has clinical and pathological features resembling age-related macular degeneration. We generated and characterised a mouse "knock-in" model carrying the Ser163Arg mutation in the orthologous murine C1qtnf5 gene by site-directed mutagenesis and homologous recombination into mouse embryonic stem cells. Biochemical, immunological, electron microscopic, fundus autofluorescence, electroretinography and laser photocoagulation analyses were used to characterise the mouse model. Heterozygous and homozygous knock-in mice showed no significant abnormality in any of the above measures at time points up to 2 years. This result contrasts with another C1qtnf5 Ser163Arg knock-in mouse which showed most of the features of L-ORMD but differed in genetic background and targeting construct.
authors: MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, Edinburgh, United Kingdom.
authors: Xinhua
authors: X
authors: Shu
authors: Ulrich F O
authors: UF
authors: Luhmann
authors: Tomas S
authors: TS
authors: Aleman
authors: Susan E
authors: SE
authors: Barker
authors: Alan
authors: A
authors: Lennon
authors: Brian
authors: B
authors: Tulloch
authors: Mei
authors: M
authors: Chen
authors: Heping
authors: H
authors: Xu
authors: Samuel G
authors: SG
authors: Jacobson
authors: Robin
authors: R
authors: Ali
authors: Alan F
authors: AF
authors: Wright
mesh_terms: D017668:Age of Onset; D019943:Amino Acid Substitution; D000818:Animals; D001483:Base Sequence; D020256:Choroidal Neovascularization / Q000209:etiology / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D003094:Collagen / Q000235:genetics*; D004195:Disease Models, Animal; D053595:Embryonic Stem Cells / Q000378:metabolism; D005260:Female; D055879:Gene Knock-In Techniques; D006367:HeLa Cells; D059765:Homologous Recombination; D006801:Humans; D007834:Lasers / Q000009:adverse effects; D008028:Light Coagulation / Q000009:adverse effects; D008268:Macular Degeneration / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D051379:Mice; D010641:Phenotype; D012160:Retina / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*
chemical_list: C487851:C1QTNF5 protein, human; D003094:Collagen