Hereditary hyperplastic gingivitis in North American farmed silver fox (Vulpes vulpes)

Abstract

Hereditary hyperplastic gingivitis is a progressive growth of gingival tissues in foxes resulting in dental encapsulation. It is an autosomal recessive condition displaying a gender-biased penetrance, with an association with superior fur quality. This disease has been primarily described in European farmed foxes. Here we document its emergence in Canada.

Hereditary hyperplastic gingivitis (HHG) presents as a tumor-like growth of the gingival tissue on the mandible and maxilla in farmed silver foxes (1), a coat color variant of the American subspecies (Vulpes vulpes fulva) of the red fox (Vulpes vulpes). It is an autosomal recessive inherited disease, with predominance in males, and is correlated with selection for superior fur quality (1). Until 2008, HHG had only been described in the farmed fox population, at which time a case in a wild red fox was reported in Germany (2). In Canada and the rest of North America this condition has never previously been documented in the fox population. We review the origins of HHG and detail its discovery and manifestation in farmed silver foxes in Newfoundland, Canada.

Fox farming in Canada originated in the late 1800’s in Prince Edward Island (PEI) with the successful raising of wild silver foxes in captivity and the pioneering of selective breeding in foxes, resulting in the first commercial production of silver fox pelts. The interest in this profitable new industry led to national distribution of breeding stock and exportation to the United States and Europe (3,4). The European fur farming industry began with the importation of 2 silver foxes from Canada to Norway in 1914. Norway went on to pioneer numerous silver fox color mutations. The first documented case of HHG in Europe was in Sweden around 1940 from a young male fox with superior fur that had been imported from Norway (1).

Since the 1940s there have been 2 main described etiologies for the silver fox gingival overgrowth, with different underlying disease mechanisms. Kull described it as a recessive gender-biased disease, more common in males than in females, in which the disease phenotype is induced by a viral infection (H. Lohi, Finnish fur specialist, personal communication, 2004). This theory was reiterated in the 1982 publication of Kangas’ book on diseases of foxes and raccoon dogs (5). In 1960, Dyrendahl and Henricson published an extensive review of HHG (1). They stated that pronounced manifestation of HHG occurs at approximately 2 to 3 years of age, with gingival proliferation continuing throughout life, resulting in dental encapsulation. They concluded that HHG was an autosomal recessive disease demonstrating incomplete penetrance, with an increased incidence in males relative to females (1). In addition, there was a pleiotropic relationship between HHG and high fur quality (typically length and density of the guard hairs) (1). Pathology indicated large epithelial extensions in the keratinized collagen of the gingival tissue. Schulze et al (2) documented the first case of HHG in the wild fox population. In this case, both macroscopic and histopathological examination confirmed the diagnosis of HHG rather than a viral-induced papillomatous growth (2). Meanwhile, despite the rapid expansion using a limited gene pool, the Canadian stock had not shown any signs of HHG before now.

In Newfoundland and Labrador, 20 male and 20 female, 10-month-old silver foxes were imported from Finland in January 2003. By May 2004, 5 of the male Finnish imported foxes were manifesting gingival proliferation. The extent of the gingival involvement varied with 1 fox displaying complete encapsulation of the incisors with symmetrical coverage extending back to the molars on both arcades of the maxilla and mandible. Neither the Finnish females nor any Canadian foxes housed in the same shed had any obvious signs of gingival proliferation. All foxes were fed a relatively soft diet of commercial fox pellets softened with water and mixed with ground chicken. All foxes appeared healthy and were in good body condition.

In June 2004 all imported Finnish foxes underwent thorough manual oral examinations. Six males were severely affected with gum tissue hyperplasia, and encapsulated teeth; 12 had mild to moderate hyperplasia, and 2 were unaffected. Seventeen of the 20 females examined showed mild to moderate gum hyperplasia that was more pronounced around the molars and premolars than the incisors. In addition, a 1-year-old male from a mating of a Finnish male to a Canadian female in 2003 clearly showed early signs of the disease. Re-examination in December 2004 demonstrated rapid progression of the hyperplasia. Severe cases also showed gingivitis, plaque-covered teeth, and irregular positioning of some teeth. Due to animal welfare concerns and the genetic implications of this disease, the severely affected animals were removed from breeding stock and pelted. In subsequent breeding seasons, the disease continued to be evident in offspring from crosses between remaining original foxes and from crosses with Canadian foxes. It was not present in every generation nor did it progress as rapidly, or develop as severely, as in the original Finnish foxes.

Two additional trips were made to Norway to obtain fox breeding stock. In December 2004 30 Norwegian males and 30 females were selected. Individual clinical examinations of prospective candidates, as well as familial examinations dating back 2 earlier generations, were performed to ascertain whether the disease was present in their pedigree. These animals, which arrived in January 2005, did not develop any signs of hyperplasia during the first year after importation but it became evident in a few, as they grew older. It was also evident in subsequent generations suggesting many of the original imports were non-symptomatic carriers. The final trip was to select 30 male Norwegian foxes with rare silver fox color mutations. These foxes were selected in December 2005 and arrived in January 2006. Again, meticulous examinations were performed on all possible candidates for acquisition but fewer familial connections were available for examination. Several of these males did show HHG within the first year after importation and many of their offspring mated with the previously imported Norwegian silver foxes did go on to manifest gingival hyperplasia.

Gross examination of the affected silver fox gingival tissue identified proliferative gingival tissue with a red granular surface (Figure 1). The tissue bled easily and profusely with minimal trauma to which the animals appeared insensitive. Surgical biopsy samples contained a rich vascular fibrous tissue that was tough and resilient when cut below the mucosa. In all affected gingiva, the hyperplastic tissue occurred outward along the lingual and buccal aspects, and then extended up or down, covering a variable amount of the crowns of the teeth. The gingival hyperplasia was initially bilaterally symmetrical, but often progressed to surround some teeth more than others. In moderate to advanced cases, the incisors were completely buried in the convergence of hyperplasic tissue from both the lingual and buccal sides. In advanced cases, the proliferative gingiva on the buccal side formed large multilobular, cauliflower-like masses that often completely obscured the teeth. Postmortem examination of the severely affected fox heads obtained after pelting in 2004 showed the hyperplastic gum tissue to be pale, lacking firm consistency with occasional areas of necrosis in the flattened multilobulated masses. Deep pockets containing food and debris were present between large gingival tissue flaps and the teeth on both the buccal and lingual sides. This provided the environment for premature periodontal disease and may explain irregular teeth placement and asymmetrical dental arcades noticed in the advanced cases.

Figure 1.

A — Original Finnish silver fox gingival overgrowth upon full examination in 2004. B — An original Finnish silver fox postmortem demonstrating gingival overgrowth resulting in dental rearrangement. C — An unaffected Canadian silver fox (Photographs by Robert Hudson).

Histological sections were taken from a variety of fox gingival samples, representing a range of gingival proliferation from normal to severe. In all affected samples, thick collagen bundles, a few fibroblast cells and small blood vessels expanded the submucosa (Figure 2). The degree of submucosal expansion ranged from mild to marked, corresponding to the degree of gingival proliferation. In all affected histology sections, the mucosa was undermined by moderate numbers of lymphocytes and plasma cells, whereas the normal gingival sections contained minimal numbers of lymphocytes and plasma cells. Based on histology the diagnosis was fibrous gingival hyperplasia ranging in severity from mild to marked.

Figure 2.

Histology slides viewed at 25× magnification of hereditary hyperplastic gingivitis (HHG) silver fox gingival samples. A — Histological presentation of mild HHG. B — Histological presentation of severe HHG. Arrow shows the thickness of the submucosa. (Photographs provided by Laura Rogers).

The Newfoundland and Labrador fox farming industry underwent rapid expansion during the 1980s with the addition of many new farms and increases in size of existing farms. Despite the increased inbreeding that resulted from the demand for more breeding stock, there was no evidence of HHG in the Newfoundland and Labrador farmed fox population until after the introduction of Scandinavian foxes in 2003. Similarly in the Maritime Provinces and the rest of Canada, a century of breeding silver foxes from the original PEI stock, as well as cross breeding with animals imported from Scandinavia, including color mutations, had not resulted in any documented cases of HHG prior to 2004. Histologically, the presence of expanded submucosa due to increased collagen in the 2004–2006 cases in Newfoundland was congruent with both the original HHG description (1) and the HHG case in wild fox, supporting the HHG diagnosis (1,2). Original HHG descriptions suggest an autosomal recessive mode of inheritance (1). Prior to the Scandinavian importation of foxes to Newfoundland and Labrador in 2004, this disease was not documented in Canada. In addition, since 2004 the disease has not been present in every subsequent generation from imported foxes, suggesting a complex process behind the development of HHG.

This disease impacts both economics and animal welfare. As this disease appears more often when selecting for superior fur quality in affected populations, it has the potential for high propagation and wide dissemination. As the etiology is genetic, the only prevention of further propagation of the disease is cessation of breeding of the affected animals and potential carriers of the genes for this disease. Also, affected animals often have to be culled prematurely before living out a normal productive life and this can have an enormous economic impact on the fox farming industry. This disease may come with a high price as animal welfare concerns are being heightened globally. Hereditary hyperplastic gingivitis also has the potential to affect wild populations creating a potential ecosystem health concern if affected or carrier animals inadvertently escape from captivity and breed with indigenous populations. The industry would benefit from a thorough understanding of the genetics of this disease as well as a commercial genetic test that could be used to help farmers select stock that are free of the undesirable gene.

Here we have described cases of HHG in a Canadian fox farm associated with the importation of Scandinavian breeding stock. The disease can still be found today in the offspring of the original imported foxes. The next step in understanding this disease is to investigate its underlying genetic mechanisms. This work is currently ongoing utilizing strategies such as candidate gene sequencing and whole genome microarray expression techniques based on canine genome resources.