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Tabby patterns of fur coats are defining characteristics in wild and domestic felids. Historically, three autosomal alleles at one locus (Tabby): Abyssinian (Ta ; a.k.a. ticked), mackerel (Tm ; a.k.a. striped) and blotched (tb ; a.k.a. classic, blotched) were thought to control these patterns in domestic cats and their breeds. Currently, at least three loci influence cat tabby markings, two of which are designated Tabby and Ticked. The Tabby locus is laeverin (LVRN) and affects the mackerel and blotched patterns. The unidentified gene for the Ticked locus on cat chromosome B1 was suggested to control the presence or absence of the ticked pattern (Tabby - Abyssinian (Ta ; a.k.a. ticked). The cat reference genome (Cinnamon, the Abyssinian) has the ticked phenotype and the variant dataset and coat phenotypes from the 99 Lives Cat Genome Consortium (195 cats) were used to identify candidate genes and variants associated with the Ticked locus. Two strategies were used to find the Ticked allele(s), one considered Cinnamon with the reference allele or heterozygous (Strategy A) and the other considered Cinnamon as having the variant allele or heterozygous (Strategy B). For Strategy A, two variants in Dickkopf Wnt Signaling Pathway Inhibitor 4 (DKK4), a p.Cys63Tyr (B1:41621481, c.188G>A) and a less common p.Ala18Val (B1:42620835, c.53C>T) variant are suggested as two alleles influencing the Ticked phenotype. Bioinformatic and molecular modeling analysis suggests that these changes disrupt a key disulfide bond in the Dkk4 cysteine-rich domain 1 or Dkk4 signal peptide cleavage respectively. All coding variants were excluded as Ticked alleles using Strategy B.

Simple Summary: Milk or mammary tissue swab samples were collected from both defective and normal udder halves in three different studies to identify the bacterial species involved. Samples were collected at different physiological time points: pre-mating, throughout lactation, at weaning and post-weaning. Numerous bacterial species were identified, with Staphylococcus species, Mannheimia haemolytica and Streptococcus being the most frequently isolated. Bacteria were isolated from at least one third (udder lumps) or more than half (hard udder) of defective udder halves, whereas no bacteria were isolated from more than two thirds of normal udder halves. Frequently isolated bacterial species tended to persist longer, whereas less frequently isolated bacterial species showed less stability over time. Bacterial species more frequently identified from defective udder halves and which appear more stable over time should be considered as a factor for making culling decisions. The objectives of these studies were to identify associations between udder half defects (hard or lump) and bacteria isolated from milk or mammary tissue swabs, to compare with samples from normal udder halves at different physiological time points and to compare bacterial species isolated via milk and swabs of mammary tissue from within the same udder halves. A total of 1054 samples were aseptically collected from each udder half of 199 non-dairy breed (Romney) ewes from three different studies (Study A, n = 77; Study B, n = 74; and Study C, n = 48). Conventional bacterial culture and MALDI-ToF mass spectrometry were used for bacterial identification. Of the 225 samples from which bacteria were isolated, Mannheimia haemolytica and Streptococcus uberis were the dominantly identified species from defective udder halves, whereas coagulase-negative staphylococcus (CNS) species, mostly Staphylococcus simulans and Staphylococcus chromogenes, were more frequently isolated from normal udder halves. The ongoing presence of bacterial species over time was variable, although less frequently identified species showed less stability over time. A very high agreement (91.5%) of bacterial species identified was observed between the mammary tissue swab and udder half milk samples during post-weaning. In summary, palpable udder half defects were associated with bacterial positivity, and the ongoing presence of the bacteria over time was dependent on the species involved. Hence, culling ewes with palpable udder half defects that had more stable bacterial species could contribute to reducing the recurrence of palpable defects or mastitis. [ABSTRACT FROM AUTHOR]

State-of-the-art health care includes genome sequencing of the patient to identify genetic variants that contribute to either the cause of their malady or variants that can be targeted to improve treatment. The goal was to introduce state-of-the-art health care to cats using genomics and a precision medicine approach. To test the feasibility of a precision medicine approach in domestic cats, a single cat that presented to the University of Missouri, Veterinary Health Center with an undiagnosed neurologic disease was whole-genome sequenced. The DNA variants from the cat were compared to the DNA variant database produced by the 99 Lives Cat Genome Sequencing Consortium. Approximately 25× genomic coverage was produced for the cat. A predicted p.H441P missense mutation was identified in NPC1, the gene causing Niemann-Pick type C1 on cat chromosome D3.47456793 caused by an adenine-to-cytosine transversion, c.1322A>C. The cat was homozygous for the variant. The variant was not identified in any other 73 domestic and 9 wild felids in the sequence database or 190 additionally genotyped cats of various breeds. The successful effort suggested precision medicine is feasible for cats and other undiagnosed cats may benefit from a genomic analysis approach. The 99 Lives DNA variant database was sufficient but would benefit from additional cat sequences. Other cats with the mutation may be identified and could be introduced as a new biomedical model for NPC1. A genetic test could eliminate the disease variant from the population.

A 7‐week‐old Labrador retriever presented for further investigation into acute onset regurgitation, following weaning from liquid to solid food. A videofluoroscopic swallow study demonstrated a severe, focal esophageal dilation in the mid‐cervical region, with marked luminal narrowing distally. Computed tomography with angiography revealed esophageal stenosis, extending from C4–T2, secondary to circumferential esophageal wall thickening. With the concern for development of secondary aspiration pneumonia, the owners elected to euthanize the dog and consented to postmortem examination. A diagnosis of segmental, cervical esophageal muscular hypertrophy was made on necropsy, consistent with the fibromuscular thickening type of congenital esophageal stenosis reported in humans. [ABSTRACT FROM AUTHOR]

Mammary gland tumors (MGTs) are common in dogs and show a variable clinical behavior that is difficult to predict. Currently, few immunohistochemical markers have been established to predict the prognosis of a canine MGT. However, p53 immunostaining has been variably reported to be prognostic for canine MGTs. Additionally, while p16CDK2NA protein (p16) immunostaining has been found to be prognostic for human breast cancers, this marker has never been evaluated as a prognostic marker for canine neoplasms. In the present study, the prognostic utility of p53 and p16 was evaluated in 35 canine malignant MGTs. It was observed that 19 (54%) dogs died due to their MGTs with an overall mean survival time (MST) of 882 days. Seven MGTs showed p53 immunostaining, but this was not significantly associated with death (4 of 7 vs. 15 of 28; p = 0.6) or MST (670 vs. 934 days; p = 0.57). Five dogs had MGTs with no p16 immunostaining, 28 MGTs had intermediate p16 immunostaining, and two MGTs had increased p16 immunostaining. Neither death due to MGT (4 of 5, 14 of 28, or 1 of 2; p = 0.28) nor MST (683, 927, and 307 days; p = 0.31) were significantly associated with p16 immunostaining. Interestingly, p53 immunostaining was significantly associated with an increase or loss of p16 immunostaining. This is the first time that p16 has been evaluated as a prognostic marker for canine neoplasms. While these results suggest that a proportion of canine MGTs develop by cellular mechanisms that alter both p53 and p16 expression, there was no evidence that defects in p53 or p16 alter the behavior of a MGT. Neither p53 nor p16 was found to significantly predict prognosis, although this could reflect the limited number of MGTs included in the study. [ABSTRACT FROM AUTHOR]

British shorthair (BSH) kittens in multiple litters died as a result of a severe non-neoplastic lymphoproliferative disease that showed many similarities with human autoimmune lymphoproliferative syndrome (ALPS). Human ALPS is caused by inherited defects in FAS-mediated lymphocyte apoptosis and the possibility of similar defects was investigated in BSH cats. The whole genomes of two affected kittens were sequenced and compared to 82 existing cat genomes. Both BSH kittens had homozygous insertions of an adenine within exon 3 of the FAS- ligand gene. The resultant frameshift and premature stop codon were predicted to result in a severely truncated protein that is unlikely to be able to activate FAS. Three additional affected BSH kittens were homozygous for the variant, while 11 of 16 unaffected, but closely related, BSH cats were heterozygous for the variant. All BSH cats in the study were from a population with significant inbreeding. The variant was not identified in a further survey of 510 non-BSH cats. Identification of a genetic defect in the FAS-mediated apoptosis pathway confirms that the lymphoproliferative disease in BSH cats fulfills the diagnostic criteria for ALPS in humans. These results will enable the development of a genetic test to detect BSH carrier animals. [ABSTRACT FROM AUTHOR]

The objectives of these studies were to identify associations between udder half defects (hard or lump) and bacteria isolated from milk or mammary tissue swabs, to compare with samples from normal udder halves at different physiological time points and to compare bacterial species isolated via milk and swabs of mammary tissue from within the same udder halves. A total of 1054 samples were aseptically collected from each udder half of 199 non-dairy breed (Romney) ewes from three different studies (Study A, n = 77; Study B, n = 74; and Study C, n = 48). Conventional bacterial culture and MALDI-ToF mass spectrometry were used for bacterial identification. Of the 225 samples from which bacteria were isolated, Mannheimia haemolytica and Streptococcus uberis were the dominantly identified species from defective udder halves, whereas coagulase-negative staphylococcus (CNS) species, mostly Staphylococcus simulans and Staphylococcus chromogenes , were more frequently isolated from normal udder halves. The ongoing presence of bacterial species over time was variable, although less frequently identified species showed less stability over time. A very high agreement (91.5%) of bacterial species identified was observed between the mammary tissue swab and udder half milk samples during post-weaning. In summary, palpable udder half defects were associated with bacterial positivity, and the ongoing presence of the bacteria over time was dependent on the species involved. Hence, culling ewes with palpable udder half defects that had more stable bacterial species could contribute to reducing the recurrence of palpable defects or mastitis.

Papillomaviruses (PVs) cause around 5% of all human cancers, including most cervical cancers and around a quarter of all oral cancers. Additionally, some studies have suggested that PVs could cause a proportion of human lung, breast, and bladder cancers. As PVs have been associated with skin cancer in cats and, more rarely, dogs, it was hypothesized that these viruses could also contribute to epithelial cancers of the lung, mammary gland, and bladder of dogs and cats. Formalin-fixed paraffin-embedded samples of 47 canine and 25 feline cancers were examined histologically for evidence of PV infection. Additionally, three sets of consensus PCR primers were used to amplify PV DNA from the samples. No histological evidence of PV infection was visible in any of the cancers. DNA from a bovine PV type was amplified from one sample, while two different samples were found to contain human PV DNA. However, these were considered to be contaminants, and no canine or feline PV types were amplified from any of the cancers. These results suggest that PVs do not frequently infect the lung, mammary gland, or bladder of dogs and cats and therefore are unlikely to be significant factors in the development of cancers in these tissues.

Mammary gland tumors (MGTs) are common in dogs and show a variable clinical behavior that is difficult to predict. Currently, few immunohistochemical markers have been established to predict the prognosis of a canine MGT. However, p53 immunostaining has been variably reported to be prognostic for canine MGTs. Additionally, while p16 CDK2NA protein (p16) immunostaining has been found to be prognostic for human breast cancers, this marker has never been evaluated as a prognostic marker for canine neoplasms. In the present study, the prognostic utility of p53 and p16 was evaluated in 35 canine malignant MGTs. It was observed that 19 (54%) dogs died due to their MGTs with an overall mean survival time (MST) of 882 days. Seven MGTs showed p53 immunostaining, but this was not significantly associated with death (4 of 7 vs. 15 of 28; p = 0.6) or MST (670 vs. 934 days; p = 0.57). Five dogs had MGTs with no p16 immunostaining, 28 MGTs had intermediate p16 immunostaining, and two MGTs had increased p16 immunostaining. Neither death due to MGT (4 of 5, 14 of 28, or 1 of 2; p = 0.28) nor MST (683, 927, and 307 days; p = 0.31) were significantly associated with p16 immunostaining. Interestingly, p53 immunostaining was significantly associated with an increase or loss of p16 immunostaining. This is the first time that p16 has been evaluated as a prognostic marker for canine neoplasms. While these results suggest that a proportion of canine MGTs develop by cellular mechanisms that alter both p53 and p16 expression, there was no evidence that defects in p53 or p16 alter the behavior of a MGT. Neither p53 nor p16 was found to significantly predict prognosis, although this could reflect the limited number of MGTs included in the study.

Female Sprague-Dawley rats (n = 100; age, 3 wk) were fed diets that included a vitamin premix and either albumin or milk powder. Rats fed the albumin diet gained weight more slowly than did the other group. Between 19 and 28 wk of being fed the albumin diet, 12 rats died of bacterial cystitis and pyelonephritis. In addition, 2 more rats from the same dietary group developed peritonitis after ovariohysterectomy. Examination of the 44 rats fed the albumin diet that completed the 34-wk experiment revealed pyelonephritis in 68%, cystitis in 66%, urolithiasis in 27%, and nephrolithiasis in 5%. Squamous metaplasia of the transitional epithelium was present in all 44 rats, although other epithelia were histologically normal. Vitamin A deficiency was diagnosed after analyses of blood and liver samples. Analysis of the vitamin premix revealed approximately 25% of the expected amount of vitamin A. Because the milk powder contained sufficient vitamin A, deficiency did not occur in rats fed the milk powder diet. The major consequences of vitamin A deficiency in the rats were squamous metaplasia, bacterial infection, and calculus formation within the urinary tract. This report illustrates the importance of careful formulation and storage of vitamin premixes used in experimental diets. Vitamin A deficiency should be considered in rats with decreased weight gain and urinary tract disease even if ocular lesions are not present.

A 3-yr-old female Flemish Giant pet rabbit developed a papilloma on the right nictitating membrane. Although the papilloma was excised surgically, it promptly recurred. Examination of the eye 10 wk after surgery revealed that in addition to the initial mass, 2 smaller papillomas were present on the lower eyelid. All 3 masses were excised, and histology revealed papillomatous hyperplasia of the conjunctival epithelium, koilocytosis, and intranuclear viral inclusions. Polymerase chain reaction amplified papillomaviral DNA from the largest papilloma. Sequencing of the amplicon revealed 99.3% homology with rabbit oral papillomavirus (ROPV). All 3 masses recurred after removal. In addition, the rabbit was noted to be losing weight. Weight loss continued until the rabbit died 3 mo later. All 3 papillomas persisted until death. This article provides the fi rst description of ROPV causing conjunctival papillomas and is the fi rst report of ROPV from the southern hemisphere. The persistence of the papillomas in this case is also unusual and may suggest that ROPV-induced conjunctival papillomas are less likely than oral papillomas to spontaneously regress. Alternatively, the death of this rabbit may indicate a compromised immune system that allowed papillomaviral persistence.