Abyssinian Cats Research Articles

Investigating the DNA binding and transactivation activity of rdyCRX as a molecular basis for retinal dysplasia in Felis catus (943.1)

In a pedigree developed from affected Abyssinian cats, an early onset rod‐cone dysplasia (Rdy) was identified and demonstrates an autosomal dominant inheritance. This is an excellent model for inherited retinal disorders such as retinitis pigmentosa (RP), cone‐rod dystrophy (CoRD), and Leber’s congenital amaurosis (LCA) because these lead to early developmental blindness via rod and cone photoreceptor dysfunction. The putative mutation for the Rdy phenotype is a single nucleotide deletion in the cone rod homeobox (CRX) protein, causing a frame shift that introduces a premature stop codon. Both normal CRX and rdyCRX proteins are expressed in vivo, suggesting a competitive interaction as the mechanism of pathology. The premature stop codon causes the truncation of the last third of the CRX protein containing the transactivational domains required for functional activity, while retaining the DNA binding domains allowing the rdyCRX to potentially compete with the normal CRX protein for binding to promoter regions. This could result in disrupting transcription initiation of genes necessary for the development and maintenance of the eye. EMSA analysis demonstrates competitive binding to Bat‐1 promoter oligonucleotide. Wild type CRX, rdyCRX, NRL, and NR2E3 have been successfully cloned in preparation of the development of a transcriptional activity assay.Grant Funding Source: Supported by HHMI

Feline atopic dermatitis: a retrospective study of 45 cases (2001–2012)

Atopic dermatitis (AD) is recognized as a common cause of pruritus in cats, but it remains incompletely characterized. The aim of the study was to evaluate cases of confirmed feline AD. Fourty-five cats from a dermatology referral practice (2001-2012). A retrospective case record review was carried out using strict diagnostic criteria, including exclusion of flea-bite hypersensitivity and adverse food reaction. Disease prevalence was 12.5%, with domestic mixed (n = 24), Abyssinian (n = 6) and Devon rex (n = 3) cat breeds predisposed. Median age of onset was 2 years (62% <3 years; 22% >7 years; range 3 months to 12 years). Common presentations were severe (82%), nonseasonal (82%), waxing/waning (36%) pruritus, with alopecia/crusting/excoriations and/or erosions/ulceration (73%). Miliary dermatitis (20%) and eosinophilic granuloma complex lesions (27%) occurred. The face/head (71%), ventral abdomen (51%), neck (51%), limbs (38%), pinnae (31%), dorsum/rump (31%) and feet (16%) were frequently affected sites; lesions were restricted to the head/neck in only five cats (11%). Concurrent otitis externa (16%), superficial bacterial pyoderma (49%), Malassezia dermatitis (7%), flea-bite hypersensitivity (24%) and adverse food reaction (13%) occurred. Strong reactions on intradermal allergen testing were common (68%; 19 of 30), most frequently to pollens (61%) and/or insects (46%). Good response to ciclosporin (100%; 10 of 10), systemic glucocorticoids (55%; 22 of 40) and allergen-specific immunotherapy (57%; 13 of 23) and good/partial response to antihistamines (67%; 22 of 33) were reported. The prevalence of feline AD was higher than previously suggested, and breed predispositions were confirmed. Severe nonseasonal pruritus was most common, with a varied spectrum of lesions affecting a range of body areas.

Distribution of αB-Crystallin in the Central Retina and Optic Nerve Head of Different Mammals and its Changes during Outer and Inner Retinal Degeneration

Purpose: To investigate species differences in the distribution and localization of alpha B-crystallin (ABC) in the normal retina and optic nerve head region, and to describe changes during outer and inner retina degeneration. Material and methods: Animals studied included mice, rats, cats, pigs, cows, and monkeys. Sections of the optic nerve and central retina were labeled with antibodies against ABC and glial fibrillary acidic protein (GFAP). Results: ABC was located in astrocytes and Muller cells with different intensities. During outer retina degeneration (dystrophic rat and Abyssinian cat), only late stages showed an increase in ABC in the retina and optic nerve head. Inner retina degeneration in the glaucoma mouse model showed no increase of ABC. In the monkey glaucoma model, only the innermost layer of the optic nerve head showed increased labeling for ABC. Conclusions: The distribution of ABC is species dependent and is (excluding the mouse) present in the nerve fiber layer of the retina and in the optic nerve head (localization of astrocytes). Chronic retinal degeneration does not necessarily lead to an over-expression of ABC. While in outer retinal degeneration induction was predominantly present in late stages, pressure-induced glaucoma led to a specific increase in ABC already in early stages indicating a local stress-response in this region.

Haematological and biochemical reference intervals of four feline breeds.

Many feline breeds have been generated from a small number of ancestors. Thus, breed-specific peculiarities can be expected, which could include haematological and biochemical measurements. Despite this, there are only a few reports on breed-specific reference intervals (RI). This information is essential in routine practice where results from individual patients are usually compared with an RI. The aim was to compare haematological and biochemical data from clinically healthy Abyssinian, Holy Birman, Norwegian Forest and Siberian cats with published RIs to assess whether the published RIs are acceptable in these breeds. Comparison with established RIs using guidelines from the National Committee for Clinical Laboratory Standards and the American Society of Veterinary Clinical Pathology, revealed a number of breed-related clinicopathological differences. New RIs were established, but in most cases the new RIs overlapped with published RIs, and the use of the breed-specific data would minimally affect the clinical interpretation of laboratory results. Important differences that could result in misinterpretation of laboratory results were as follows: microcytosis and high α2-globulin concentrations in Abyssinian cats; high serum creatinine, α2-globulin and glucose concentrations in Holy Birman cats; high serum alkaline phosphatase activity and calcium and phosphate concentration in Norwegian Forest cats; low β2-globulin and γ-globulin concentrations in Norwegian Forest and Siberian cats. Breed-specific RIs should be used for these analytes. In addition, care should be taken in interpreting clinicopathological data in purebred cats for which specific RIs have not been established.

A High-Resolution 15,000Rad Radiation Hybrid Panel for the Domestic Cat

The current genetic and recombination maps of the cat have fewer than 3,000 markers and a resolution limit greater than 1 Mb. To complement the first-generation domestic cat maps, support higher resolution mapping studies, and aid genome assembly in specific areas as well as in the whole genome, a 15,000_Rad radiation hybrid (RH) panel for the domestic cat was generated. Fibroblasts from the female Abyssinian cat that was used to generate the cat genomic sequence were fused to a Chinese hamster cell line (A23), producing 150 hybrid lines. The clones were initially characterized using 39 short tandem repeats (STRs) and 1,536 SNP markers. The utility of whole-genome amplification in preserving and extending RH panel DNA was also tested using 10 STR markers; no significant difference in retention was observed. The resolution of the 15,000_Rad RH panel was established by constructing framework maps across 10 different 1-Mb regions on different feline chromosomes. In these regions, 2-point analysis was used to estimate RH distances, which compared favorably with the estimation of physical distances. The study demonstrates that the 15,000_Rad RH panel constitutes a powerful tool for constructing high-resolution maps, having an average resolution of 40.1 kb per marker across the ten 1-Mb regions. In addition, the RH panel will complement existing genomic resources for the domestic cat, aid in the accurate re-assemblies of the forthcoming cat genomic sequence, and support cross-species genomic comparisons.

Retinal capillary morphology in the Abyssinian cat with hereditary retinal degeneration

Retinal capillary morphology in the Abyssinian cat with hereditary retinal degeneration

Erythrocyte Pyruvate Kinase Deficiency mutation identified in multiple breeds of domestic cats

BackgroundErythrocyte pyruvate kinase deficiency (PK deficiency) is an inherited hemolytic anemia that has been documented in the Abyssinian and Somali breeds as well as random bred domestic shorthair cats. The disease results from mutations in PKLR, the gene encoding the regulatory glycolytic enzyme pyruvate kinase (PK). Multiple isozymes are produced by tissue-specific differential processing of PKLR mRNA. Perturbation of PK decreases erythrocyte longevity resulting in anemia. Additional signs include: severe lethargy, weakness, weight loss, jaundice, and abdominal enlargement. In domestic cats, PK deficiency has an autosomal recessive mode of inheritance with high variability in onset and severity of clinical symptoms.ResultsSequence analysis of PKLR revealed an intron 5 single nucleotide polymorphism (SNP) at position 304 concordant with the disease phenotype in Abyssinian and Somali cats. Located 53 nucleotides upstream of the exon 6 splice site, cats with this SNP produce liver and blood processed mRNA with a 13 bp deletion at the 3’ end of exon 5. The frame-shift mutation creates a stop codon at amino acid position 248 in exon 6. The frequency of the intronic SNP in 14,179 American and European cats representing 38 breeds, 76 western random bred cats and 111 cats of unknown breed is 6.31% and 9.35% when restricted to the 15 groups carrying the concordant SNP.ConclusionsPK testing is recommended for Bengals, Egyptian Maus, La Perms, Maine Coon cats, Norwegian Forest cats, Savannahs, Siberians, and Singapuras, in addition to Abyssinians and Somalis as well an any new breeds using the afore mentioned breeds in out crossing or development programs.

Génétique de la couleur et de la texture du pelage chez le chat domestique

Genetics of coat colour and texture in domestic cats Recent progresses in canine and feline genomics have led to the identification of an increasing number of loci, genes and mutations in these two species. Canine genetics was the first to benefit from new methodological and molecular tools, but feline genetics is slowly catching up. The whole genome sequencing of an Abyssinian cat achieved in 2007 paved the way for considerable progress. About forty genes involved in feline inherited diseases and traits of interest have been identified to date. Coat colour and texture are the most commonly identified traits of interest at the molecular level. Genetic tests are now available for these colours and textures, and help feline breeders select sires and dams to produce the desired kittens.

Hepatoblastoma in a Cat

Hepatoblastomas are neoplasms that originate from putative pluripotential stem cells of the liver. A hepatic mass from an 8-year-old Abyssinian cat was composed of cords and sheets of neoplastic cells, with scattered rosettes and small ductal structures. Most neoplastic cells had a pale eosinophilic cytoplasm and a round to ovoid nucleus. The tumor also had short spindle cells with an oval nucleus. Immunohistochemically, neoplastic cells were weakly positive for embryonic hepatocellular markers, such as alpha-fetoprotein and cytokeratin (CK) 8/18, but negative for the hepatocellular marker Hepatocyte Paraffin 1. The cells were also positive for CD56/neural cell adhesion molecule and for the biliary epithelial markers CK 7, CK 8/18, CK CAM5.2, and vimentin, but negative for CK 20. Some neoplastic cells expressed neuroectodermal or neuroendocrine markers, such as protein gene product 9.5 and synaptophysin, but were negative for chromogranin A and not argyrophilic by the Grimelius technique. The cat died soon after the biopsy without clinical improvement.

Nutritional secondary hyperparathyroidism in two cats

Two three-month-old, intact female Abyssinian cats were presented with a history of lameness, constipation and ataxia. The cats had been fed a diet composed almost exclusively of meat. Both showed severe osteopenia and multiple pathological fractures on radiography. Following euthanasia of the more severely affected cat, postmortem examination revealed changes consistent with nutritional secondary hyperparathyroidism and fibrous osteodystrophy, such as cortical thinning, massive connective tissue invasion in the diaphysis of long bones, and hypertrophy of the chief cells in both parathyroid glands. After introducing a balanced commercial diet to the surviving cat, bone mineralisation improved from the baseline value, and at subsequent examinations at three, six and 22 weeks later, as indicated by bone mineral density measurements obtained by dual-energy X-ray absorptiometry and computed tomography.

Widespread retinal degenerative disease mutation (rdAc) discovered among a large number of popular cat breeds

The recent discovery of a mutational variant in the CEP290 gene (CEP290: IVS50+9T>G), conferring recessive retinal degeneration in Abyssinian and Somali (long-haired Abyssinian) cats (rdAc) prompted a survey among 41 cat breeds (846 individuals) to assess the incidence, frequency and clinical consequence of rdAc. The rdAc allele displayed widespread distribution, observed in 16/43 (37%) breeds, exhibiting a high allele frequency (∼33%) in North American and European Siamese populations. Clinical evaluations demonstrated high concordance between rdAc pathology and the CEP290 (IVS50+9T>G) homozygous genotype (P=1.1E-6), with clinical disease similar to affected Abyssinians/Somalis. This retinal degeneration has not been reported in breeds other than the Abyssinian/Somali and poses a significant health risk particularly in the Siamese breed group. Alertness of the veterinary community and the present availability of commercial diagnostic testing could synergistically enable breeders to reduce the incidence of rdAc blindness in pure-bred cat populations.

Retinal degeneration in the Abyssinian and Somali cat (rdAc): correlation between genotype and phenotype and rdAc allele frequency in two continents

To characterize hereditary retinal degeneration in the Abyssinian cat (rdAc) in a recently established closed colony segregating for the rdAc mutation, and evaluate possible differences in the age of onset and progression of disease phenotype since the initial description of rdAc 25 years ago. The sample size of an earlier study was increased in order to determine the allele frequency in Abyssinian and Somali cats on a worldwide basis. Twenty rdAc affected cats from the closed animal facility, 87 Abyssinian and Somali cats for study of genotype-phenotype concordance, and DNA from 131 Abyssinian and Somali cats from Scandinavia, the UK and Australia for evaluation of the rdAc allele frequency. DNA was extracted from blood and buccal swabs using commercially available kits, followed by genotyping. Ophthalmic examinations were performed in the USA and Sweden by two board-certified veterinary ophthalmologists. A greater variation in the age of onset and progression of the disease was observed compared to that previously described. An excellent correlation between genotype and phenotype was observed. A population genetic survey revealed that the rdAc allele is in moderate abundance in the Abyssinian breed in Europe and Australia. Surprisingly, homozygosity for the mutant allele was observed in a Siamese cat with ophthalmoscopic findings similar to those originally described for affected rdAc individuals. Alertness to the potential of rdAc is needed on the part of the veterinary ophthalmology community, not only in Abyssinian and Somali cats but possibly also in other related cat breeds.

Functional and structural assessment of retinal sheet allograft transplantation in feline hereditary retinal degeneration

To investigate whether sheets of fetal retinal allografts can integrate into the dystrophic Abyssinian cat retina with progressive rod cone degeneration. Fetal retinal sheets (cat gestational day 42), incubated with BDNF microspheres, were transplanted to the subretinal space of four cats at an early disease stage. Cats were studied by fundus examinations, bilateral full-field flash ERGs, and indocyanine green and fluorescein angiograms up to 4 months following surgery. E42 donor and transplanted eyes were analyzed by histology and immunohistochemistry for retinal markers. Funduscopy and angiography showed good integration of the transplants in two of four cats, including extension of host blood vessels into the transplant and some scarring in the host. In these two, transplants were found in the subretinal space with laminated areas, with photoreceptor outer segments in normal contacts with the host retinal pigment epithelium. In some areas, transplants appeared to be well-integrated within the host neural retina. Neither of these two cats showed functional improvement in ERGs. In the other two cats, only remnants of donor tissue were left. Transplants stained for all investigated cellular markers. No PKC immunoreactivity was detected in the fetal donor retina at E42, but developed in the 4-month-old grafts. Fetal sheet transplants can integrate well within a degenerating cat retina and develop good lamination of photoreceptors. Functional improvement was not demonstrated by ERG in cats with well-laminated grafts. Transplants need to be further evaluated in cat host retinas with a more advanced retinal degeneration using longer follow-up times.

Calcium-phosphorus homeostasis and changes in parathyroid hormone secretion in cats with various stages of spontaneous chronic renal failure

Feline chronic renal failure was recognized with increased frequency in Maine coon, Abyssinian, Siamese, Russian blue, and Burmese cats. The objective of this study was to investigate the relationship between parathyroid hormone (PTH) level, calcium, and phosphorus homeostasis and the development of various stages of the naturally occurring chronic renal failure (CRF) in cats. Thirty-two CRF cats without history of receiving special diet for renal diseases that were presented to the Small Animal Hospital, Faculty of Veterinary Science, Chulalongkorn University were studied. Nineteen CRF cats were followed prospectively for 60 days and divided into two groups: uremic group (11 cats) and end-stage group (eight cats). The control group (13 cats) were normal cats, which were brought for vaccination at the same hospital within the same period. CRF cats with blood urea nitrogen concentrations of more than 50 mg/dl, serum creatinine level of more than 2.1 mg/dl, and urine specific gravity of between 1.008 and 1.014 were included into the study. Completed blood count, blood chemistry, electrolytes, including sodium, potassium, total calcium, and phosphorus, and PTH levels were measured on days 0, 14, 30, and 60 after the first diagnosis. The results showed that cats with CRF had significantly lower red blood cells, hemoglobin, and pack cell volume than control cats (p < 0.01) on days 0, 14, 30, and 60. PTH levels on first day of diagnosis were 50.51 ± 19.65, 79.41 ± 28.12, and 183.37 ± 50.12 pg/ml in controls, uremic, and end-stage groups, respectively. Cats in end-stage group had significantly increased levels of PTH when compared to control (p < 0.01) and uremic groups (p < 0.05) on days 0, 14, and 30. Serum phosphorus levels also increased significantly in end-stage group (p < 0.001), indicating the presence of renal secondary hyperparathyroidism. This study reveals that PTH level is significantly increased in end-stage CRF cats who did not received special diet for renal diseases. The development of renal secondary hyperparathyroidism in end-stage CRF cats significantly decreased its survival rate.

Erythrocytic pyruvate kinase deficiency and AB blood types in Australian Abyssinian and Somali cats

To determine the frequency of the mutant pyruvate kinase (PK) allele, haematological parameters and AB blood types of Abyssinian and Somali cats in Australia. Complete blood cell and reticulocyte counts, DNA PK mutation testing and blood typing were performed in all cats. A total of 60 cats (36 Abyssinians, 24 Somalis) were included (37 females, 23 males). For the mutant PK allele, three female Somalis were homozygous (affected, 5%), 17 cats were heterozygous (carrier, 28%) and 40 cats tested negative (normal, 67%). Pedigree analysis revealed common ancestry of affected and many carrier cats. Of affected cats, two had regenerative anaemias and all had reticulocytosis (range 64-390 x 10(9)/L; P < 0.001 compared with normal or carrier cats). The only consistent historical sign was lethargy. One affected cat was euthanased 18 months after testing, because of anaemia, neutropenia, anorexia and weight loss. The mutant allele frequency was 0.19 overall (0.29 in Somalis, 0.13 in Abyssinians). All cats had blood type A. The commercial blood typing card method incorrectly identified 12 cats as having type AB blood. The frequency of the mutant PK allele is high in Australia. Screening for PK deficiency is indicated before mating and in individual cats of these breeds, even in the absence of anaemia and especially when there is reticulocytosis. Although all cats in the present study had blood type A, blood type B is common in these breeds worldwide. Retyping of any AB typed cats by a laboratory technique is recommended.

IN THIS ISSUE – January/February 2009

Laboratory reference intervals for Merino lambs ▪ Intradermal cetrimide for nonsurgical mulesing ▪ Carprofen with intradermal cetrimide ▪ Polioencephalomalacia in cattle grazing Brassica plants ▪ Dietary antibiotics for proliferative enteropathy ▪ First description of equine pneumonitis and fetal loss (EPFL) in Australia ▪ Pyruvate kinase deficiency in Abyssinian and Somali cats ▪ Suspected neuropathic pain in dogs ▪ Osteosarcoma of the canine penile bone ▪ Pre weaning morbidity in llamas and alpacas ▪ Previously unreported species of microsporidium in Western Pigmy perch ▪ Granulomatous disease in a nestling parrot ▪ Uterine adenomyosis in an orang‐utan

Persistent haematuria and proteinuria due to glomerular disease in related Abyssinian cats.

Eight cases of glomerular disease in young, related Abyssinian cats are described. Haematuria was the most consistent feature. Six cats developed the nephrotic syndrome. The short-term prognosis was good for cats with haematuria and fair for cats with the nephrotic syndrome as oedema resolved in three of the six cats. Light microscopic examination of renal biopsies from three cats was considered normal or revealed only mild abnormalities. In the three cases subjected to necropsy, histological abnormalities included mild mesangial hypercellularity and adhesions between the glomerular tuft and Bowman's capsule consistent with a focal proliferative glomerulopathy. Further investigation into this glomerulopathy will require ultrastructural and immunohistochemical studies to characterise the glomerular abnormality and genetic analyses to investigate its potential to be an inherited disease. Glomerular disease, potentially a familial one, should be considered in the investigation of persistent haematuria or proteinuria in Abyssinian and related cats.

Clinical course of pyruvate kinase deficiency in Abyssinian and Somali cats.

The objective of this study was to examine clinical signs, laboratory parameters, and course of disease in Abyssinian and Somali cats with pyruvate kinase (PK) deficiency. The clinical course of 25 PK-deficient cats was followed over a time period of 0.8-11.3 years (median 4.3). Eleven cats (age 0.8-7.8 years, median 4.4) did not show signs according to the owners. In 14 cats (age 0.1-5 years, median 1.7) the owners noted lethargy (10), diarrhoea (seven), pale mucous membranes (six), inappetence (six), poor coat quality (six), weight loss (four), icterus (four), and pica (two). Sixteen cats had been used for breeding at least once before diagnosis. Laboratory abnormalities included anaemia (70%), increased aggregated reticulocyte counts (94%), hyperglobulinaemia (80%), hyperbilirubinaemia (53%), and increased liver enzymes (47%). Six of 25 affected cats died (four) or were euthanased (two) at ages ranging from 1.3 to 11.3 years (median 4.1) presumably because of PK-deficiency. These findings emphasise that PK deficiency shows variation in age of onset and severity of signs. As PK-deficient cats can be asymptomatic testing for PK deficiency before breeding is strongly recommended.

Choroidal microcirculation in Abyssinian cats with hereditary rod–cone degeneration

Blood flow in the choroid of eyes with retinal degeneration is normally reduced. In the Abyssinian cat, where no changes in choroidal blood flow were observed recently, a closer morphological analysis revealed that two factors might have lead to this finding. (a) The cat's eye consists of a tapetum lucidum where 15.5μm microspheres cannot reach the precapillary branching in contrast to the non-tapetal areas, where microspheres were located right next to the choriocapillaris. This fact has not yet been described and might be important for further physiological measurements in eyes of species with a tapetum lucidum. (b) The tapetal cells themselves might have a protective role for the choriocapillaris and RPE during retinal degeneration in this specific animal model. Even in late stages of retinal degeneration the RPE and choriocapillaris in areas covered by the tapetum lucidum were not affected whereas non-tapetal areas showed loss of RPE and capillaries.

Neural precursors isolated from the developing cat brain show retinal integration following transplantation to the retina of the dystrophic cat

The cat has served as an important nonrodent research model for neurophysiology and retinal degenerative disease processes, yet very little is known about feline neural precursor cells. To culture these cells and evaluate marker expression, brains were dissected from 45-day-old fetuses, enzymatically dissociated, and grown in the presence of EGF, bFGF and PDGF. Expanded cells widely expressed nestin, Sox2, Ki-67, fusin (CXCR4) and vimentin, while subpopulations expressed A2B5, GFAP, or beta-III tubulin. Precursors prelabeled with BrdU and/or transduced with a recombinant lentivirus that expresses GFP were transplanted subretinally in five dystrophic Abyssinian cats. Two to 4 weeks following surgery, histology showed survival of grafted cells in three of the animals. Labeled cells were found in the neuroretina and RPE layer, as well as in the vitreous and the vicinity of Bruch's membrane. There was no evidence of an immunologic response in any of the eyes. Neural precursor cells can therefore be cultured from the developing cat brain and survive as allografts for up to 4 weeks without immune suppression. The feasibility of deriving and transplanting feline neural precursor cells, combined with the availability of the dystrophic Abyssinian cat, provide a new feline model system for the study of retinal repair.