A KCNJ10 mutation previously identified in the Russell group of terriers also occurs in Smooth-Haired Fox Terriers with hereditary ataxia and in related breeds

Background

Hereditary ataxias with similar phenotypes were reported in the Smooth-Haired Fox Terrier, the Jack Russell Terrier and the Parson Russell Terrier. However, segregation analyses showed differing inheritance modes in these breeds. Recently, molecular genetic studies on the Russell group of terriers found independent mutations in KCNJ10 and CAPN1, each associated with a specific clinical subtype of inherited ataxia. The aim of this study was to clarify whether or not Smooth-Haired Fox Terriers with hereditary ataxia and dogs of other related breeds harbor either of the same mutations. A sub goal was to update the results of KCNJ10 genotyping in Russell group terriers.

Findings

Three Smooth-Haired Fox Terriers with hereditary ataxia and two Toy Fox Terriers with a similar phenotype were all homozygous for the KCNJ10 mutation. The same mutation was also found in a heterozygous state in clinically unaffected Tenterfield Terriers (n = 5) and, in agreement with previous studies, in Jack Russell Terriers, Parson Russell Terriers, and Russell Terriers.

Conclusions

A KCNJ10 mutation, previously associated with an autosomal recessive spinocerebellar ataxia in Jack Russell Terriers, Parson Russell Terriers, and Russell Terriers segregates in at least three more breeds descended from British hunting terriers. Ataxic members of two of these breeds, the Smooth-Haired Fox Terrier and the Toy Fox Terrier, were homozygous for the mutation, strengthening the likelihood that this genetic defect is indeed the causative mutation for the disease known as “hereditary ataxia” in Fox Terriers and “spinocerebellar ataxia with myokymia, seizures or both” in the Russell group of terriers.     

Cataract in the West Highland White Terrier

Cataracts were found in 49 of 97 interrelated West Highland White Terriers. Thirty-four dogs exhibited a ‘y’ suture cataract, mainly affecting the tips of the posterior ‘y’ suture line, while 12 dogs had complete cataracts. An autosomal recessive inheritance is surmised.     

Diagnostic ultrasonography of equine lens and posterior segment abnormalities

Purpose To define the indications for equine ocular ultrasonography and to provide representative ultrasonographic images of lens and posterior segment diseases. Methods Retrospective study. Equine medical records dating from January 1983 to March 2001 were reviewed. All cases that: (1) had a lens and/or posterior segment abnormality; and (2) received a complete ophthalmic examination and ocular ultrasonography were included. Results Forty‐three cases (n = 64 eyes) out of 112 total cases of equine lens and/or posterior segment abnormalities qualified. The following conditions were identified ultrasonographically in order of decreasing frequency: cataracts, vitreal opacities, retinal detachment, lens luxation, endophthalmitis, microphthalmos, choroiditis, lens rupture, lenticonus, buphthalmos and phthisis bulbi. Ultrasonography often enabled diagnoses to be made in the presence of anterior opacities in both surgical (pre and/or postoperatively) and nonsurgical cases. Additional ocular conditions were identified in adults with cataracts more frequently than in foals with cataracts. Conclusions Cataracts were the most common lens abnormality identified in horses that received ocular ultrasound examination. Cataracts were commonly found in association with other ocular abnormalities. Ultrasonography was a practical and effective method of evaluating the lens and posterior segment, particularly in cases with anterior opacities. Ultrasonography also provided critical information with regard to the potential for surgical removal of cataracts and was a valuable component of postsurgical follow‐up.     

Cataracts in Labrador Retriever and Jack Russell Terrier From the United Kingdom: A Two-Year Retrospective Study

Cataracts are among the most common ocular diseases, and are a leading cause of vision loss in humans and dogs. Jack Russell Terriers (JRT) and Labrador Retrievers (LR) are among the most popular canine breeds in the United Kingdom, and also among the most affected by cataracts.This study aimed to analyze the clinical features and the surgical outcome of cataracts in JRT and LR in an ophthalmologic reference Veterinary Hospital in the United Kingdom. For that purpose, medical records from JRT and LR diagnosed with cataracts between January 2015 and December 2016 were retrospectively evaluated. Data related to identification, clinical history, preoperative features, and surgical outcomes were analyzed.Forty-four dogs (81 eyes), including 26 JRT and 18 LR, were enrolled in the study. Mean ages were 10.2 ± 3.2 years in JRT and 8.5 ± 3.7 years in LR. Twenty-eight (63.6%) were females and 16 (36.4%) were males. Most dogs (84.1%) presented with bilateral cataracts. Nuclear and cortical cataracts were the most prevalent type in both breeds (JRT: n?=?30, 61.2%; LR: n?=?16, 50.0%), although subcapsular cataracts were also frequent in LR (n?=?10, 31.3%). Significant differences in cataract location within the lens were detected between the two breeds (P?=?.002).Senile in JRT (n?=?7) and genetic in LR (n?=?7) were the most common etiologies. Concomitant ocular lesions were more frequent in dogs presented with cataracts in advanced stages, and included lens (n?=?18; JRT: n?=?15; LR: n?=?3) and retinal alterations (n?=?8; JRT: n?=?2; LR: n?=?6), and glaucoma (n?=?6; JRT: n?=?5; LR: n?=?1). Thirty-three animals (75.0%, 51 eyes) were submitted to phacoemulsification with intraocular lens placement. Of these, 28 eyes (54.9%; JRT: n?=?21; LR: n?=?7) were visual, 19 eyes (37.3%; JRT: n?=?11; LR: n?=?8) presented impaired vision and four eyes (7.8%; JRT: n?=?0; LR: n?=?4) were blind at last clinical record. Postoperative complications were detected in 11 eyes (21.6%), and were more frequent in dogs presented with cataracts in advanced stages.These results and the multifactorial nature of cataracts call for further studies to identify and characterize the variables in a broader assessment, including other breeds and influencing factors.     

Primary lens luxation in the Chinese Shar Pei: clinical and hereditary characteristics

A pedigree analysis of a family of 15 related Chinese Shar Peis was conducted. This pedigree analysis, including affected and nonaffected dams, sires and offspring, was compiled to document and characterize the occurrence, common clinical signs, and age of onset of primary lens luxation while suggesting a possible mode of inheritance in this breed. Of the five offspring from the mating of an affected dam to two unrelated affected males, 100% of offspring were affected with bilateral primary lens luxations. Of the four viable offspring from the mating of the same affected dam to an unrelated, unaffected male, two dogs (50%) were affected. The average age of onset of affected animals (seven) in this first generation was 4.9 years (range 3–6 years). The six dogs in the second generation of the same pedigree line were 2-years-old at examination with none of these animals affected at the time of this study. The most common presenting complaints were a unilateral change in ocular appearance (5 of 7 dogs) and subjective vision impairment (4 of 7 dogs). The most common clinical sign upon ophthalmic examination was iridodonesis (unilateral 4 of 7 dogs; bilateral 3 of 7 dogs) and the presence of an aphakic crescent (3 of 7 dogs). Gonioscopy and tonometry of severely affected eyes revealed a narrow or closed iridocorneal angle and ocular hypertension. This study suggests that primary lens luxation does occur in the Chinese Shar Pei, resembling the clinical condition (age of onset, clinical signs) previously described in the terrier breeds, the Border Collie, and the Tibetan Terrier. Application of the phenotypic findings in this study to a Mendelian genetic model of inheritance suggests that primary lens luxation in the Chinese Shar Pei is inherited as a simple autosomal recessive trait.     

Evaluation of canine heat shock transcription factor 4 (HSF4) as a candidate gene for primary cataracts in the Dachshund and the Entlebucher Mountain dog

OBJECTIVE: Testing of the cataract-causing insertion/deletion mutation in the canine HSF4 gene for its linkage and association with primary cataracts (CAT) in Dachshunds and Entlebucher Mountain dogs. MATERIALS: Exon 9 with flanking intronic regions of the canine HSF4 gene was sequenced in 24 Dachshunds and 20 Entlebucher Mountain dogs. The HSF4 cDNA sequence of lens tissue was analyzed in a CAT-unaffected mixed-breed dog and in three CAT-affected dogs of different breeds, including a Wire-haired Dachshund, a Dachshund-mix and a German Shepherd dog. RESULTS: In all dogs investigated here, the previously reported CAT-causing mutation did not exist. We found a single nucleotide polymorphism (SNP) in intron 9, which was neither associated nor linked with the CAT phenotype in the two dog breeds. CONCLUSION: The CAT phenotype in the two dog breeds investigated here was not caused by the same mutation found to be associated with early-onset CAT in the Staffordshire Bull Terrier and Boston Terrier. The intronic SNP may be useful to test HSF4 for linkage with CAT in further dog breeds.     

Case Report Cutaneous vasculitis in five Jack Russell Terriers

Abstract A new, possibly breed associated, vasculitis of Jack Russell Terriers is described. Lesions include alopecia and focal crusted ulcers of the distal extremities and bony prominences. Histopathological lesions include single cell necrosis of the epithelium, pigmentary incontinence, leucocytoclastic vasculitis and ischaemic degeneration of hair follicles. Dermal oedema and an infiltrate of lymphocytes and/or macrophages are often seen. Clinically and histopathologically the disease most closely resembles dermatomyositis of Collies and Shetland sheepdogs but the obvious breed discrepancy makes systemic lupus erythematosus the most likely differential diagnosis. Dapsone and anti-inflammatory doses of prednisone have proved to be satisfactory treatments. Résumé— Une nouvelle dermatose à prédisposition raciale, de type vascularite est décrite chez des jack russel terriers. Les lésions cliniques incluent une alopécie, des ulcèrations focales et croûteuses des extrémités distales et des points de pression. Les lésions histolopathologiques montrent des nécroses isolées des kératinocytes, une incontinence pigmentaire, une vascularite leucocytoclasique et une dégénérescence ischémique des follicules pileux. Un oedème dermique et une infiltration lymphocytaire et/ou macrophagique sont également observés. Sur les plans clinique et histopathologique, cette maladie ressemble plus aux dermatomyosites du Colley et du Shetland, mais la discordance raciale évidente fait du lupus érythémateux systémique le diagnostic différentiel le plus vraisemblable. La dapsone et la prednisone à dose antiinflammatoire sont des traitements satisfaisants. [Parker, W.M., Foster, R.A. Cutaneous vasculitis in five Jack Russell Terriers (Vascularite cutanée chez 5 jack russel terriers). Veterinary Dermatology 1996; 7 : 109–115.] Resumen Se describe una vasculitis nueva, posiblemente asociada a la raza en el terrier Jack Russell. Las lesiones incluyen alopecia y ulceraciones costrosas en las extremidades distales y en prominencias óseas. Las lesiones histopatológicas incluyen necrosis celular individual del epitelio, incontinencia pigmentaria, vasculitis leucocitoclástica y degeneración isquémica de los foliculos pilosos. Con frecuencia se observa edema dérmico y una infiltración por linfocitos y/o macrófagos. Este cuadro se asemeja clinica e histopatológicamente a la dermatomiositis de los perros Collie y Shetland pero la distancia obvia entre estas razas hace que el diagnóstico diferencial más probable sca el de lupus eritematoso sistémico. Se consiguieron tratamientos satisfactorios con Dapsona y dosis antiinflamatorias de prednisona. [Parker, W.M., Foster, R.A. Cutaneous vasculitis in five Jack Russell Terriers (Vasculitis cutánea en cinco Terriers Jack Russell). Veterinary Dermatology 1996; 7 : 109–115.] Zusammenfassung— Es wird eine neue, möglicherweise rasseabhängige Vaskulitis bei Jack Russell Terriern beschrieben. Die Veränderungen bestehen in Alopezie, fokalen verkrusteten Geschwüren der distalen Extremitäten und Knochevorsprünge. Histopathologische Veränderungen bestehen in Einezelzellnekrose des Epithels, Pigmentinkontinenz, leukozytoklastischer Vaskulitis und ischämischer Degeneration der Haarfollikel. Dermales ödem und Lymphozyten- und/oder Makrophageninfiltrate werden häufig beobachtet. Klinisch und histopathologisch ähnelt die Erkrankung sehr der Dermatomyositis von Collie und Sheltie, aber die offensichtliche Rassendiskrepanz läßt den systemischen Lupus erythematosus als wahrscheinlichste Differentialdiagnose erscheinen. Dapson und entzündungshemmende Dosen von Prednison zeigten sich als ausreichende Behandlung. [Parker, W. M., Foster, R. A. Cutaneous vasculitis in five Jack Russell Terriers (Kutane Vaskulitis bei fünf Jack Russell Terriern). Veterinary Dermatology 1996; 7 : 109–115.]     

Evaluation of risk factors for development of secondary glaucoma in dogs: 156 cases (1999-2004)

OBJECTIVE: To determine the immediately antecedent cause of secondary glaucoma and the prevalence of secondary glaucoma with anterior uveitis or lens dislocation in dogs. DESIGN: Retrospective case series. ANIMALS: 156 dogs with secondary glaucoma. PROCEDURES: Cause of glaucoma was determined from records. Breed, age, sex, and neuter status of all dogs with secondary glaucoma were compared with the general hospital population. The prevalence of secondary glaucoma in dogs with a primary diagnosis of lens dislocation or anterior uveitis during the same period was determined. RESULTS: Secondary glaucoma was diagnosed in 156 of 2,257 (6.9%) dogs examined because of ophthalmic disease and was bilateral in 33 (21.2%) of those dogs. In 31 (94%) bilaterally affected dogs, the antecedent cause was the same in both eyes. Common causes of secondary glaucoma were non-surgical anterior uveitis (44.9%), anterior uveitis associated with prior phacoemulsification (15.8%), and lens dislocation (15.2%). Parson Russell Terriers, Poodles, Boston Terriers, Cocker Spaniels, Rhodesian Ridgebacks, and Australian Cattle Dogs had diagnoses of secondary glaucoma more often than expected, compared with the reference population. Age, sex, neuter status, and laterality were not associated with secondary glaucoma. The prevalence of secondary glaucoma in dogs with lens dislocation or uveitis was 15% or 17%, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Glaucoma develops secondary to many intraocular diseases, particularly uveitis and lens dislocation. Diagnosis of these diseases should prompt frequent monitoring of intraocular pressure, regardless of signalment.     

Identification of mutations in HSF4 in dogs of three different breeds with hereditary cataracts

Cataracts are a leading cause of blindness in both dogs and humans. Mutations in several genes have been associated with inherited forms of human cataract, but no mutations have been identified as the cause of any form of canine inherited cataract. We have used a candidate gene approach to investigate 20 genes, known to be associated with cataract in humans, for their potential association with the development of hereditary cataract (HC) in dogs. We have identified mutations in the HSF4 gene in Staffordshire Bull Terriers, Boston Terriers and Australian Shepherds affected by HC. Interestingly, different mutations in this single gene may be causing a recessive form of cataract in Staffordshire Bull Terriers and Boston Terriers and a dominant cataract in Australian Shepherds. Identification of the mutations that cause HC in these three breeds provides a method of controlling the disease within populations at risk using a simple diagnostic test, and also establishes cataract in these breeds as models for their human counterparts.     

Genetic analysis of presumed inherited eye diseases in Tibetan Terriers

We analysed the systematic environmental influences and the additive genetic variation for the presumed inherited eye diseases (PIED), membrana pupillaris persistens, distichiasis, primary lens luxation, non-congenital cataract, and progressive retinal atrophy, in Tibetan Terriers. Data were obtained from the International Kennel Club for Tibetan dog breeds in Germany. PIED were recorded in the years 1987 to 2001 by standardised protocols of the Dortmunder Kreis, the association for diagnosis of inherited eye diseases in animals (DOK). The material included 849 Tibetan Terriers from 596 litters in 203 different kennels. The multivariate linear animal model using residual maximum likelihood methods regarded the fixed effects of sex, birth year, experience of the veterinary ophthalmologist, litter size, percentage of examined dogs per litter, inbreeding coefficient, and age at examination. The common environment of the litter and the additive genetic effect of the animal were taken into account as randomly distributed effects. The heritability estimates for PIED in Tibetan Terriers were h2=0.17+/-0.04 (membrana pupillaris persistens), h2=0.04+/-0.03 (distichiasis), h2=0.13+/-0.04 (primary lens luxation), h2=0.13+/-0.04 (non-congenital cataract), and h2=0.49+/-0.08 (progressive retinal atrophy). The additive genetic correlation between non-congenital cataract and progressive retinal atrophy was highly positive rg=0.76+/-0.11, while that between membrana pupillaris persistens and progressive retinal atrophy rg=-0.43+/-0.14 was highly negative. The number of examinations performed by the veterinary ophthalmologists was associated with higher heritabilities for non-congenital cataract and progressive retinal atrophy. We concluded from our analysis that all investigated PIED in Tibetan Terriers are genetically influenced.     

Primary lens instability in ten related cats: clinical and genetic considerations

Objectives : To describe bilateral lens instability in 10 related domestic shorthair cats over three generations. Methods : Complete ophthalmic examinations were performed. Lentectomies were carried out. Sections of affected lenses focused on the equatorial area were examined by transmission electron microscopy. The potential involvement of several candidate genes (ADAMTS17, ADAMTSL4, ADAMTS10 and FBN1) known to be associated with lens luxation in other species was investigated. Results : The group of animals included 10 related cats, nine of them being affected by lens instability over three generations. Transmission electron microscopy showed the presence of zonular material at the lens equator. Signs of lens instability were not associated with other ocular disease. Analysis of the pedigree suggests a dominantly inherited condition. A mutation in ADAMTS17 was excluded, but a possible association between the condition and a microsatellite flanking FBN1 indicates this gene should be considered a strong candidate responsible for primary lens luxation in this pedigree. Clinical Significance : These observations suggest an inherent zonular defect unrelated to extraneous factors. The family relationship is compatible with a possible genetic basis, and the pedigree suggests that the condition could be dominant. Data also suggest the mutation in the FBN1 gene could be responsible for primary lens luxation in this pedigree of cats.     

Factor X deficiency in a Jack Russell terrier

Deficiency in factor X (Stuart-Prower factor) was identified in a 7-month-old spayed female Jack Russell Terrier following recurrent bleeding episodes. Various relatives were screened for factor X deficiency and low and subnormal levels were identified in the father and paternal grandmother, respectively. Factor X deficiency has been previously documented in a family of American Cocker Spaniels, in which the inheritance pattern appeared to be an autosomal dominant trait with variable expression. This is the first report describing this coagulopathy in the Jack Russell Terrier.     

Inheritance of cataract in the Bichon Frise

OBJECTIVE: To determine the mode of inheritance of cataract formation in the Bichon Frise. MATERIALS: Thirty-six closely related Bichon Frise dogs in a pedigree of 61 dogs were examined using slit-lamp biomicroscopy and indirect ophthalmoscopy over a period of 10 years. RESULTS: Of the 61 related dogs, 36 were examined repeatedly. Twelve cataractous dogs were diagnosed (three males and nine females). Cataractous dogs resulted from matings between unaffected parents, and when one parent was cataractous and the other parent was unaffected. Age at onset of cataract formation ranged from 18 to 160 months. Available information suggests that the cataracts are inherited as an autosomal recessive trait. CONCLUSION: Cataracts appear inherited in the Bichon Frise as an autosomal recessive trait. Additional cataract x cataract matings are necessary to confirm the autosomal recessive heredity.     

ADAMTS17 mutation associated with primary lens luxation is widespread among breeds

Primary lens luxation (PLL) is a well-recognized, painful and potentially blinding inherited ocular condition in dogs. We screened PLL-affected dogs of 30 different breeds, to identify those which carried a previously described c.1473+1 G>A mutation in ADAMTS17 that is associated with PLL in Miniature Bull terriers, Lancashire Heelers, and Jack Russell terriers. This ADAMTS17 mutation was identified in PLL-affected dogs from 14 additional breeds. PLL-affected dogs from some breeds (most notably the Shar pei and the Brittany spaniel) did not carry the G1473+1A ADAMTS17 mutation, indicating they must suffer from a genetically distinct form of the condition. We also estimated the frequency of this ADAMTS17 mutation in some of the breeds. Our findings indicate the mutation segregates in a large number of different breeds of dog, many of which are terriers or breeds with terrier co-ancestry, but some of which have more diverse origins. Our results also indicate that the mutation is present at high frequency within most of the breeds in which it segregates. In the miniature bull terrier breed estimates of mutation frequency ranged from 0.27 to 0.39, corresponding to 7.3-15.2% PLL-affected dogs in this breed. We also identified an increased risk of PLL associated with heterozygosity at ADAMTS17, suggesting that carriers carry a low risk of developing PLL.     

Surgical management of suspected congenital luxation of the radial head in three dogs

Abstract

CASE HISTORIES: Three dogs, aged between 11 and 20 weeks, were presented with unilateral forelimb lameness, with an associated bony prominence on the lateral elbow.

CLINICAL FINDINGS AND DIAGNOSIS: Radiographs revealed a caudolateral luxation of the radial head in all cases, consistent with a diagnosis of suspected congenital luxation of the radial head. Surgical reduction and stabilisation involved open reduction of the radial head, and in two cases the use of a trans articular pin.

CLINICAL RELEVANCE: Congenital luxation of the radial head is an uncommon condition that has conflicting reports in the literature regarding its cause, heritability, breed predisposition, treatment and prognosis. The three cases here occurred in young dogs of English Bull Terrier, Jack Russell Terrier, and Staffordshire Bull Terrier breeds. Surgical reduction and stabilisation provided successful outcomes, in all cases. Only six cases of congenital luxation of the radial head managed surgically have previously been reported in the literature.     

Molecular pathology of severe combined immunodeficiency in mice, horses, and dogs

Severe combined immunodeficiency (SCID) is an inherited disorder of humans, mice, horses, and dogs, in which affected individuals are incapable of generating antigen-specific immune responses. It occurs when lymphocyte precursors fail to differentiate into mature lymphocytes because of mutations within recombinase-activating genes 1 and 2 or within the genes encoding deoxyribonucleic acid (DNA)-dependent protein kinase (DNA-PK). It also occurs when differentiated lymphocytes are incapable of completing signal transduction pathways because of defects in cell surface receptors for interleukins (IL). A spontaneous mutation in DNA-PKcs of BALB/c mice results in SCID, as do experimentally induced mutations in RAG1 and RAG2. SCID in horses results from a spontaneous mutation in DNA-PKcs. Two molecular mechanisms account for SCID in dogs. Jack Russell Terriers have a mutation within the DNA-PKcs gene, whereas Cardigan Welsh Corgi and Basset Hound have different defects in the gene encoding the gamma chain that is common to the receptors for IL-2, -4, -7, -9, -15, and -21. The location of the mutation within target genes influences the spectrum of diseases observed in affected animals.     

A retrospective report of 90 dogs with suspected cane toad (Bufo marinus) toxicity

OBJECTIVE: To report the clinical characteristics of toad toxicity in domestic dogs in Brisbane. DESIGN: A retrospective analysis of clinical cases. PROCEDURE: All cases of toad poisoning which presented to a northern suburbs emergency clinic in Brisbane over a 30-month period beginning in April 1999 were reviewed. RESULTS: A total of 90 canine cases of suspected toad poisoning were reviewed. Small breed dogs accounted for 76% of cases. Jack Russell, Silky, and Fox Terriers were the most represented breeds. Cases were reported year round, with fewest cases over the winter months. The most common clinical signs were increased salivation (78% of cases), and red oral mucous membranes (63% cases). Seizures occurred in 31% of cases. Generally the outcome was excellent with 96% survival.     

Autosomal recessive severe combined immunodeficiency of Jack Russell terriers.

Because of unexplained mortality among 33 sibling offspring of a single pair of dogs, a family of Jack Russell Terriers was investigated. Twelve pups, 5 male and 7 female, died between 8 and 14 weeks of age. Six of those animals died in the field within 50 hours following vaccination with modified live vaccines. Subsequent histopathologic examination revealed the absence of splenic white pulp in 4 dogs and hepatic inclusions diagnostic for adenoviral infection in 2 dogs. Two additional litters yielded 2 pups with the same splenic and hepatic lesions. These observations led to a detailed study of 7 siblings whelped specifically for this investigation. Four of these 7 siblings had a profound lymphopenia and a decrease in serum immunoglobulins. Six of these dogs were necropsied at 7 weeks of age, and 4 of them had marked hypoplasia of all lymphoid tissue. The affected pups had an 86% decrease in mean thymic weight, with poor corticomedullary differentiation, and very few CD3-positive (T cell) thymocytes were detected immunohistochemically. However, the affected thymic tissue stained intensely with a immunochemical stain for cytokeratin. The other affected lymphoid tissues were identified histologically only by stromal architectural characteristics. Lymph nodes lacked both CD3 and CD79a (B cell) positive cells. The analyzed breeding data were consistent with an autosomal recessive mode of inheritance. This canine severe combined immunodeficiency has immunologic and pathologic features similar to those observed in immunodeficient C.B-17 mice and Arabian horses.