Association of the FGF4L2 retrogene with fibrocartilaginous embolic myelopathy in dogs
Abstract Background Fibrocartilaginous embolic myelopathy (FCE) is a well‐documented condition in dogs although rarely reported in chondrodystrophic breeds. Genetic associations have not been defined. Objectives Define the association of the chondrodystrophy‐associated FGF4L2 retrogene with histopat...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2024-01-01
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| Series: | Journal of Veterinary Internal Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1111/jvim.16925 |
| _version_ | 1797349493150056448 |
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| author | Colleen Embersics Danika Bannasch Kevin Batcher Elizabeth C. Boudreau Molly Church Andrew Miller Simon Platt Jey Koehler Natasha Olby John Rossmeisl Daniel Rissi Robert Grahn Jonas Donner Peter J. Dickinson |
| author_facet | Colleen Embersics Danika Bannasch Kevin Batcher Elizabeth C. Boudreau Molly Church Andrew Miller Simon Platt Jey Koehler Natasha Olby John Rossmeisl Daniel Rissi Robert Grahn Jonas Donner Peter J. Dickinson |
| author_sort | Colleen Embersics |
| collection | DOAJ |
| description | Abstract Background Fibrocartilaginous embolic myelopathy (FCE) is a well‐documented condition in dogs although rarely reported in chondrodystrophic breeds. Genetic associations have not been defined. Objectives Define the association of the chondrodystrophy‐associated FGF4L2 retrogene with histopathologically confirmed cases of FCE. Animals Ninety‐eight dogs with a histopathologic diagnosis of FCE. Methods Retrospective multicenter study. Dogs were genotyped for the FGF4L2 and FGF4L1 retrogenes using DNA extracted from formalin‐fixed, paraffin‐embedded tissue. Associations between breed, FCE and retrogene status were investigated with reference to a hospital population and known breed and general population allele frequencies. Results FGF4L2 genotype was defined in 89 FCE cases. Fibrocartilaginous embolic myelopathy was present in 22 dogs from FGF4L2‐segregating breeds with allele frequencies of ≥5%; however, all dogs were wild type. Two Labrador retrievers with FCE carried FGF4L2 alleles. Frequency of the FGF4L2 allele was significantly (P < .001) and negatively associated with FCE relative to predicted hospital‐population dogs. FCE was overrepresented in Boxer, Great Dane, Yorkshire Terrier, Bernese Mountain Dog, Miniature Schnauzer, Rottweiler, and Shetland Sheepdog breeds. Conclusions and Clinical Importance Study data based on genotypically and histopathologically defined cases support the historical observation that FCE is uncommon in chondrodystrophic dog breeds. FGF4 plays an important role in angiogenesis and vascular integrity; anatomical studies comparing chondrodystrophic and non‐chondrodystrophic dogs might provide insight into the pathogenesis of FCE. |
| first_indexed | 2024-03-08T12:31:07Z |
| format | Article |
| id | doaj.art-42d56cddd64141cabef9706fa059b4f8 |
| institution | Directory Open Access Journal |
| issn | 0891-6640 1939-1676 |
| language | English |
| last_indexed | 2024-03-08T12:31:07Z |
| publishDate | 2024-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Veterinary Internal Medicine |
| spelling | doaj.art-42d56cddd64141cabef9706fa059b4f82024-01-22T02:05:50ZengWileyJournal of Veterinary Internal Medicine0891-66401939-16762024-01-0138125826710.1111/jvim.16925Association of the FGF4L2 retrogene with fibrocartilaginous embolic myelopathy in dogsColleen Embersics0Danika Bannasch1Kevin Batcher2Elizabeth C. Boudreau3Molly Church4Andrew Miller5Simon Platt6Jey Koehler7Natasha Olby8John Rossmeisl9Daniel Rissi10Robert Grahn11Jonas Donner12Peter J. Dickinson13Veterinary Medical Teaching Hospital, UC Davis School of Veterinary Medicine University of California, Davis Davis California USADepartment of Population Health and Reproduction University of California, Davis Davis California USADepartment of Population Health and Reproduction University of California, Davis Davis California USADepartment of Small Animal Clinical Sciences Texas A&M School of Veterinary Medicine & Biomedical Sciences College Station Texas USADepartment of Pathobiology University of Pennsylvania, School of Veterinary Medicine Philadelphia Pennsylvania USADepartment of Biomedical Sciences Cornell University College of Veterinary Medicine Ithica New York USAVetoracle Teleneurology Athens Georgia USADepartment of Pathobiology Auburn University College of Veterinary Medicine Auburn Alabama USADepartment of Clinical Sciences North Carolina State University College of Veterinary Medicine Raleigh North Carolina USADepartment of Small Animal Clinical Sciences Virginia‐Maryland College of Veterinary Medicine Blacksburg Virginia USADepartment of Pathology University of Georgia College of Veterinary Medicine Athens Georgia USAVeterinary Genetics Laboratory University of California, Davis Davis California USAWisdom Panel Research Team, Wisdom Panel Helsinki FinlandDepartment of Surgical and Radiological Sciences University of California, Davis Davis California USAAbstract Background Fibrocartilaginous embolic myelopathy (FCE) is a well‐documented condition in dogs although rarely reported in chondrodystrophic breeds. Genetic associations have not been defined. Objectives Define the association of the chondrodystrophy‐associated FGF4L2 retrogene with histopathologically confirmed cases of FCE. Animals Ninety‐eight dogs with a histopathologic diagnosis of FCE. Methods Retrospective multicenter study. Dogs were genotyped for the FGF4L2 and FGF4L1 retrogenes using DNA extracted from formalin‐fixed, paraffin‐embedded tissue. Associations between breed, FCE and retrogene status were investigated with reference to a hospital population and known breed and general population allele frequencies. Results FGF4L2 genotype was defined in 89 FCE cases. Fibrocartilaginous embolic myelopathy was present in 22 dogs from FGF4L2‐segregating breeds with allele frequencies of ≥5%; however, all dogs were wild type. Two Labrador retrievers with FCE carried FGF4L2 alleles. Frequency of the FGF4L2 allele was significantly (P < .001) and negatively associated with FCE relative to predicted hospital‐population dogs. FCE was overrepresented in Boxer, Great Dane, Yorkshire Terrier, Bernese Mountain Dog, Miniature Schnauzer, Rottweiler, and Shetland Sheepdog breeds. Conclusions and Clinical Importance Study data based on genotypically and histopathologically defined cases support the historical observation that FCE is uncommon in chondrodystrophic dog breeds. FGF4 plays an important role in angiogenesis and vascular integrity; anatomical studies comparing chondrodystrophic and non‐chondrodystrophic dogs might provide insight into the pathogenesis of FCE.https://doi.org/10.1111/jvim.16925caninechondrodystrophyFCEfibroblast growth factor |
| spellingShingle | Colleen Embersics Danika Bannasch Kevin Batcher Elizabeth C. Boudreau Molly Church Andrew Miller Simon Platt Jey Koehler Natasha Olby John Rossmeisl Daniel Rissi Robert Grahn Jonas Donner Peter J. Dickinson Association of the FGF4L2 retrogene with fibrocartilaginous embolic myelopathy in dogs Journal of Veterinary Internal Medicine canine chondrodystrophy FCE fibroblast growth factor |
| title | Association of the FGF4L2 retrogene with fibrocartilaginous embolic myelopathy in dogs |
| title_full | Association of the FGF4L2 retrogene with fibrocartilaginous embolic myelopathy in dogs |
| title_fullStr | Association of the FGF4L2 retrogene with fibrocartilaginous embolic myelopathy in dogs |
| title_full_unstemmed | Association of the FGF4L2 retrogene with fibrocartilaginous embolic myelopathy in dogs |
| title_short | Association of the FGF4L2 retrogene with fibrocartilaginous embolic myelopathy in dogs |
| title_sort | association of the fgf4l2 retrogene with fibrocartilaginous embolic myelopathy in dogs |
| topic | canine chondrodystrophy FCE fibroblast growth factor |
| url | https://doi.org/10.1111/jvim.16925 |
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