Select Page

2017 – EPI Microbiome Research

June 2017 Epi4Dogs collaborated and co-authored with Texas A&M Gastrointestinal Lab on TWO research projects. Abstracts below:

1.  June 2017Dogs with Exocrine Pancreatic Insufficiency have Dysbiosis and Abnormal Fecal Lactate and Bile Acid Concentrations

A.B. Blake1, B.C. Guard1, J.B. Honneffer1, F.G. Kumro1, O.C. Kennedy2, J.A. Lidbury3, J.M. Steiner1, J.S. Suchodolski3

1Gastrointestinal Laboratory, College of Veterinary Medicine, Texas A&M University, College station, Texas, USA, College Station, TX, USA, 2Epi4Dogs Foundation, Inc., Farmville, VA, Farmville, VA, USA, 3Gastrointestinal Laboratory, Texas A&M University, College station, TX, USA

It has been reported that dogs with exocrine pancreatic insufficiency (EPI) commonly have intestinal dysbiosis. However, the effects of EPI on microbial metabolism are poorly understood. The aim of this study was to compare fecal dysbiosis as well as fecal lactate and bile acid concentrations between dogs with EPI and healthy control dogs.

Fecal samples were collected from eleven dogs with EPI that had not received antibiotics for at least 3 weeks and had been on enzyme supplementation for 0.5–10 years (median 5 years). Fecal samples from healthy dogs (n = 18), collected for three consecutive days and pooled, served as control samples. DNA was extracted and analyzed by qPCR for selected bacterial groups and data expressed as Dysbiosis Index (as previously reported). Fecal lactate was measured by enzymatic methods (D-/L-lactic acid kit, R-Biopharm) and bile acids were quantified with gas chromatography/mass spectrometry from lyophilized feces. The Mann-Whitney U test was used to compare the Dysbiosis Index and fecal lactate and bile acid concentrations between dogs with EPI and healthy control dogs. Correlations were assessed using Spearman’s correlation coefficient and significance was set at P < 0.05.

Dogs with EPI had a higher Dysbiosis Index (median [min-max]: +3.08 [−7.29 to +7.62]) than healthy control dogs (−3.81 [−7.57 to +3.32]; P = 0.0232). Total fecal lactate concentrations were increased in dogs with EPI (3.44 mM [0.71–158.30 mM]) compared to healthy control dogs (1.14 mM [0.54–6.64 mM]; P = 0.0037). The proportion of secondary bile acid was lower in dogs with EPI (70% [6–96%]) compared to healthy control dogs (93% [12–97%]; P = 0.0431). There was no correlation between any measurements and duration of enzyme therapy.

In conclusion, this study identified differences in the fecal microbiota as well as fecal lactate and bile acid concentrations between dogs with EPI and healthy control dogs.

2.  June 2017: Fecal Fatty Acid Concentrations in Dogs with Exocrine Pancreatic Insufficiency Receiving Enzyme Supplementation

J.B. Honneffer1, A.B. Blake1, J.C. Parambeth1, O.C. Kennedy2B.C. Guard1, J.A. Lidbury3, J.M. Steiner1, J.S. Suchodolski3

1Gastrointestinal Laboratory, College of Veterinary Medicine, Texas A&M University, College station, Texas, USA, College Station, TX, USA, 2Epi4Dogs Foundation, Inc., Farmville, VA, Farmville, VA, USA, 3Gastrointestinal Laboratory, Texas A&M University, College station, TX, USA

Exocrine pancreatic insufficiency (EPI) is a disease characterized by insufficient synthesis and secretion of pancreatic enzymes by the exocrine pancreas, resulting in malassimilation of macro-nutrients. For example, insufficient pancreatic lipase prevents normal digestion of dietary fat. Consequently, EPI would be expected to be associated with excessive fat (e.g., fatty acids) remaining in the feces. Treatment of EPI includes oral supplementation of pancreatic digestive enzymes and is often effective at decreasing severity of clinical signs, but it is unclear if assimilation normalizes concomitantly. This study evaluated fecal fatty acid (FA) concentrations in dogs with EPI undergoing enzyme supplementation. The hypothesis of this study was that fecal fatty acid concentrations would be increased in dogs with EPI compared to those of healthy dogs, even when being treated with enzyme supplementation.

Fatty acid concentrations were quantified in fecal samples from 34 dogs diagnosed with EPI that were being treated with pancreatic enzyme supplements and from 82 healthy control dogs using an in-house gas chromatography/mass spectrometry (GC/MS) assay. Target analytes included palmitic acid (16:0), stearic acid (18:0), oleic acid (18:1ω9), linoleic acid (18:2ω6), α-linolenic acid (18:3ω3), gondoic acid (20:1ω9), and erucic acid (22:1ω9). A Mann-Whitney U test was used for comparison between groups. P-values were adjusted for multiple comparisons and statistical significance was set at P < 0.05.

Fecal FAs were significantly increased in the feces of dogs with EPI (all P < 0.001). Concentrations of FAs for dogs with EPI vs. healthy control dogs were (median [min-max] μg/mg of lyophilized feces): palmitic acid (12.0 [1.6–48.4] vs. 4.2 [1.3–13.4]), stearic acid (6.6 [1.1–43.2] vs. 2.3 [0.9–14.4]), oleic acid (13.8 [1.8–70.2] vs. 4.0 [0.3–16.9]), linoleic acid (10.3 [1.7–34.5] vs. 4.0 [0.4–29.7]), α-linolenic acid (1.0 [0.2–5.5] vs. 0.4 [0.1–3.5]), gondoic acid (0.69 [0.10–2.36] vs. 0.19 [0.03–0.61]), and erucic acid (0.07 [0.02–0.96] vs. 0.03 [0.01–0.27]). The sum of measured fecal FAs was 46.8 [9.0–174.6] vs. 15.3 [4.0–61.3].

Fecal fatty acid concentrations were increased in dogs with EPI, even while being treated with pancreatic enzyme supplementation. These data are consistent with malassimilation of fat in these patients.

2015 – EPI Genetics Research (Corgis)

 
JUNE 2015 ANIMAL GENETICS PUBLICATION
 

Association of DLA-DQB1 alleles with exocrine pancreatic insufficiency in Pembroke  Welsh Corgis

  1. J. M. Evans1,
  2. K. L. Tsai1,
  3. A. N. Starr-Moss1,
  4. J. M. Steiner2 and
  5. L. A. Clark1,*

Article first published online: 19 JUN 2015

 
DOI: 10.1111/age.12317
 
Exocrine pancreatic insufficiency (EPI) is a digestive disorder resulting from the insufficient secretion of enzymes from the pancreas. In dogs, this condition is often attributed to pancreatic acinar atrophy, wherein the enzyme-producing acinar cells are believed to be destroyed through an autoimmune process. Although EPI affects many diverse breeds, to date, molecular studies have been limited to the German Shepherd dog. A recent study of major histocompatibility genes in diseased and healthy German Shepherd dogs identified both risk and protective haplotypes. Herein, we genotyped DLA-DQB1 in Pembroke Welsh Corgis to determine whether dog leukocyte antigen alleles contribute to the pathogenesis of EPI across dog breeds. We evaluated 14 affected and 43 control Pembroke Welsh Corgis, which were selected based on an age of onset similar to German Shepherd dogs. We identified one protective allele (odds ratio = 0.13, P-value = 0.044) and one risk allele (odds ratio = 3.8, P-value = 0.047). As in German Shepherd dogs, the risk allele is a duplication of DLA-DQB1 (alleles DQB1*013:03 and 017:01); however, Pembroke Welsh Corgis have acquired a single polymorphism on DQB1*017:01. Thus, the DLA-DQB1 duplication is a risk allele for EPI in at least two breeds.
 

2015 – EPI Starch Research

To read the research in its entirety, please go to:  https://pdfs.semanticscholar.org/4bc4/ea4fad5af5fd8ac26d2931f7760c98dc26f1.pdf

Research Article
Starch Origin and Thermal Processing Affect Starch Digestion in
a Minipig Model of Pancreatic Exocrine Insufficiency
Anne Mößeler,1 Sandra Vagt,1 Martin Beyerbach,2 and Josef Kamphues1
1
Institute for Animal Nutrition, University of Veterinary Medicine Hannover, Foundation, Bischofsholer Damm 15,
30173 Hannover, Germany
2
Department for Biometry, Epidemiology, and Information Processing, University of Veterinary Medicine Hannover,
Foundation, Bunteweg 2, 30559 Hannover, Germany ¨
Correspondence should be addressed to Anne Moßeler; anne.moesseler@tiho-hannover.de ¨
Received 15 October 2014; Revised 21 January 2015; Accepted 22 January 2015
Academic Editor: Paul Enck

Copyright © 2015 Anne Moßeler et al. This is an open access article distributed under the Creative Commons Attribution License, ¨
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Although steatorrhea is the most obvious symptom of pancreatic exocrine insufficiency (PEI), enzymatic digestion of protein and
starch is also impaired. Low praecaecal digestibility of starch causes a forced microbial fermentation accounting for energy losses
and meteorism. To optimise dietetic measures, knowledge of praecaecal digestibility of starch is needed but such information from
PEI patients is rare. Minipigs fitted with an ileocaecal fistula with (?=3) or without (?=3) pancreatic duct ligation (PL) were used
to estimate the rate of praecaecal disappearance (pcD) of starch. Different botanical sources of starch (rice, amaranth, potato, and
pea) were fed either raw or cooked. In the controls (C), there was an almost complete pcD (>92%) except for potato starch (61.5%)
which was significantly lower. In PL pcD of raw starch was significantly lower for all sources of starch except for amaranth (87.9%).
Thermal processing increased pcD in PL, reaching values of C for starch from rice, potato, and pea. This study clearly underlines the
need for precise specification of starch used for patients with specific dietetic needs like PEI. Data should be generated in suitable
animal models or patients as tests in healthy individuals would not have given similar conclusions.

 

Abstract

Exocrine pancreatic insufficiency (EPI) is a disorder wherein the pancreas fails to secrete adequate amounts of digestive enzymes. In dogs, EPI is usually the consequence of an autoimmune disease known as pancreatic acinar atrophy. Originally believed to be a simple autosomal recessive disorder, a test-breeding recently revealed that EPI has a more complex mode of inheritance. The contributions of multiple genes, combined with environmental factors, may explain observed variability in clinical presentation and progression of this disease. Research efforts aim to identify genetic variations underlying EPI to assist breeders in their efforts to eliminate this disease from their breed and provide clinicians with new targets for therapeutic intervention and/or disease prevention. Genome-wide linkage, global gene expression, and candidate gene analyses have failed to identify a major locus or genetic variations in German Shepherd Dogs with EPI. Recently, genome-wide association studies revealed numerous genomic regions associated with EPI. Current studies are focused on alleles of the canine major histocompatibility complex. In this article we review findings from scientific investigations into the inheritance and genetic cause(s) of EPI in the purebred dog.

 

 

2009 – EPI Genetics (breeding)

RESEARCHER COMMENTS  (Dr. Leigh Anne Clark’s Corner)

June 2009: “EPI does have a genetic/heritable component, but it is likely more complex than autosomal recessive. In fact, a test breeding in Europe between
2 affected dogs resulted in a litter with NO affected puppies. Most likely there are environmental factors (stress, virus, etc.) or multiple genes contributing.
Unfortunately, 
this means that there is no accurate way to identify carriers. Definitely do not breed affected dogs, and do not repeat matings that produced
EPI. It may also 
be safest to not line breed dogs that are “carriers.” 

2010 – EPI Heritability Research

Brief Communication – J Vet Intern Med 2010;24:450–452
Heritability of Exocrine Pancreatic Insufficiency in
German Shepherd Dogs

E. Westermarck, S.A.M. Saari, and M.E. Wiberg

Brief Communication – J Vet Intern Med 2010;24:450–452
Heritability of Exocrine Pancreatic Insufficiency in
German Shepherd Dogs

E. Westermarck, S.A.M. Saari, and M.E. Wiberg

Background: Several studies have revealed that exocrine pancreatic insufficiency (EPI) is an inherited disease in German
Shepherd Dogs (GSDs). Pedigree analyses have suggested an autosomal recessive inheritance model.
Objective: Test mating of 2 dogs with EPI.
Animals: A sire and dam purebred GSD both with EPI and a litter of 6 puppies.
Methods: Test mating and long-term follow-up of offspring. The pancreas was biopsied via laparotomy on 26 occasions.
Serum trypsin-like immunoreactivity was measured. Study was approved by Animal Ethics Committee.
Results: During the 12-year study period only 2 of the 6 offsprings developed pancreatic acinar atrophy (PAA). In 1 puppy,
end-stage PAA and in the other puppy partial PAA was diagnosed.
Conclusions and Clinical Importance: PAA is not a congenital disease in GSDs. This study provided evidence that PAA is
not inherited in a simple autosomal recessive fashion.
Key words: Biopsy; Pancreatic acinar atrophy; Polygenic inheritance; Test mating; Trypsin-like immunoreactivity.

Abbreviations:
EM electron microscopy
EPI exocrine pancreatic insufficiency
GSD German Shepherd Dog
PAA pancreatic acinar atrophy
TLI trypsin-like immunoreactivity

Canine exocrine pancreatic insufficiency (EPI) is a disease characterized by inadequate production of digestive enzymes by pancreatic acinar cells. Affected dogs typically show such clinical signs as polyphagia, weight loss, yellowish poorly digested loose and pulpy feces, increased fecal volume, and frequent defecation.1. EPI has been reported in many breeds, but it is most commonly seen in German Shepherd Dogs (GSDs). In GSDs, the underlying cause of EPI is pancreatic acinar
atrophy (PAA). A characteristic of PAA is selective destruction of the digestive enzyme producing acinar cells.1, PAA has features of autoimmune disease, including genetic suspectibility to disease. 1.2.

Several studies have indicated that EPI is an inherited disease in GSDs, and most research of the inheritance model by pedigree analysis suggests that EPI is inherited in an autosomal recessive fashion.3–5 The prevalence of affected dogs in most reports has, however, been lower (!15%) than expected 25% for a simple autosomal recessive trait; thus, a polygenic mode of inheritance has been proposed.4 The mutation or candidate gene has not been identified.6.

Materials and Methods
This study was performed during 1987 to 2000. Both parents were purebred GSDs (dam 4 years, sire 6 years), with different progenitors. EPI diagnosis for both parents was documented on the basis of results of the serum trypsin-like immunoreactivity (TLI) assay 7. (dam 0.9 mg/L; sire 0.8 mg/L; control 5.2–35.0 mg/L). The dogs were fed regular commercial dog food twice daily, and 50 g of raw pig pancreas was added to every meal.

At the time of mating, both dogs were clinically in good condition. The dam delivered 9 puppies, but 3 died immediately or a short time after birth. Necropsy was performed on these puppies, and histologic examination of the pancreas did not reveal abnormalities.

Of the 6 remaining puppies, 4 were females and 2 males. The puppies were weaned at 6 weeks of age and released to their owners.

The puppies were raised in private homes. The owners were informed orally about EPI and were also provided with a written information package. They were told that the dogs would likely be afflicted with EPI. The investigators and the dog owners maintained close ties throughout the study. All of the dogs lived in the Helsinki area.

Two clinically healthy Beagles were included as control dogs. The dogs were sacrificed for an unrelated research project at the age of 3
years. The experimental protocol was approved by the Ethics Committee for Animal Experiments of the College of Veterinary Medicine, Helsinki, Finland.

Tests Performed on the Puppies
Serum TLI was measured by radioimmunoassay.7. The tests were performed for the 1st time at 6 weeks of age.

The biopsies from the pancreas were taken via laparotomy under general anesthesia. The gross appearance of pancreas was evaluated. One biopsy specimen was obtained from the right duodenal limb of the pancreas at each time point by ligation of a piece of pancreatic tissue (ca. 4.0mm in diameter) through a ventral midline abdominal incision. From all puppies the 1st biopsy was taken at 6 weeks of age and subsequently at approximately 0.5, 1.2, 2.0 years of age. Besides puppy no. 2 at 5.5 and 7.0 years of age. The biopsy specimens for histologic an electron microscopy (EM) examinations were processed in a routine manner.8. The EM findings of acinar cells were classified into 4 stages.8.

Necropsy was performed on all dogs, and several samples of the pancreas were examined. The pancreas of 2 control dogs was also studied.

Results
The dam developed a fatal mesenteric torsion 6 months after parturition. The sire was euthanized at the age of 12 years. Necropsy of both the dogs revealed a severely atrophic pancreas typical of an end-stage PAA.

The results for puppy no. 1 have been published in detail elsewhere.8 Briefly, the female puppy was clinically healthy at birth and throughout adolescence, and grew normally without signs of maldigestion. The 1st biopsy from the pancreas at the age of 6 weeks was histological normal, but EM examination revealed mild stage 1 abnormalities. The dog was clinically normal at 22 months of age, but serum TLI was decreased to 0.3 mg/L (o2.5 mg/L indicating EPI; normal reference range 5.2–
35.0 mg/L). Examination of the pancreas indicated no gross or histologic abnormalities, but EM revealed widespread degenerative changes (stages 2–4). One month
later, the dog developed typical clinical signs of EPI, and at 25 months of age the gross and histologic examination of the pancreas revealed typical features of PAA.2 Treatment with powdered pancreatic extracta and antibiotics was introduced, with good treatment response.

Puppy no. 2 (female) was clinically healthy during the 1st 5 years. Laparotomy was performed 4 times (at 1.5, 5,14, and 24 months of age). Gross and histologic examination was normal every time, and EM studies revealed stage 1 changes. Serum TLI was measured 12 times, and on 2 occasions the TLI value was subnormal (3.4 and 4.1 mg/L).

At the age of 5.5 years, the dog was still clinically healthy and of normal weight, but serum TLI was abnormally low (2.1 mg/L) and at laparotomy, the gross
examination showed partial atrophy of the pancreas. There were scattered areas of pancreas that had lost their glandular appearance and changes typical for partial
PAA resulting from atrophic lymphocytic pancreatitis.1,2 Lymphocytic inflammation was most extensive in the border zone areas of normal and partially affected tissue.
EM showed evidence of atrophy, mainly type 3 and 4 degenerative changes. The islet cells were normal.

The dog was treated with immunosuppressives (prednisolon  and azathioprined).9 Prednisolon treatment was discontinued after 1 year and azathioprine treatment
after 1.5 years.

The dog lived another 6 years after diagnosis of partial AA. No signs of EPI were present. Serum TLI was measured 11 times; the values were always o5.2 mg/L, 5
times being abnormally low, o2.5 mg/L (range 0.2–2.4 mg/L).

The dog died of internal hemorrhage at the age of 12 years. At necropsy the pancreas was severely diminished in size and histologic examination showed mild lymphocytic pancreatitis, especially in the border zone regions. In areas of more advanced tissue destruction, the findings were similar to those found in end-stage PAA.

Puppy nos. 3 to 6 showed no clinical signs typical of EPI during their lifetime. A laparotomy was performed 4 times on each dog (between 6 weeks and 24 months of age), and the pancreas on every occasion was grossly normal, and a biopsy was taken. Histologic examinations revealed a normal pancreas. EM of the biopsies often
showed type 1 changes in acinar cells. After each laparotomy, recovery was uncomplicated and postoperative assays of serum amylase and lipase activities provided
no indication of pancreatitis or pancreatic tissue damage. Serum TLI was measured 7 to 15 times, and in each dog the value was at least once subnormal. The lowest values in dog nos. 3 to 6 were 2.7, 3.4, 3.4, and 4.9 mg/L, respectively. The dogs died due to different causes at ages 8 to 13 years. At necropsy, the pancreas was grossly and histologically normal in each dog.

The TLI value of the 2 control dogs (7.5 and 8.4 mg/L) was within the normal range, and necropsy of the dogs revealed a normal pancreas both grossly and histologically. EM study of the control samples revealed evidence of type 1 changes.

Discussion
Several previous studies have suggested that EPI is inherited in an autosomal recessive fashion. Here, when 2 affected EPI dogs were mated, only 2 of the 6 offspring
revealed atrophic changes in the exocrine part of the pancreas. This is much less than expected if a disease is inherited by Mendelian genetics. A polygenic mode of
inheritance is therefore the only explanation for this outcome. This is, however, a logical result as PAA in GSDs has been shown to be an autoimmune disease.2
Performing test mating in dogs is laborious, particularly in late-onset diseases such as EPI. Test matings have been used more often in early-onset diseases, but also in these cases the keeping of affected animals purely for test purposes is ethically problematic. Fortunately, EPI is a treatable disease, and with medication an affected dog can live a more or less normal life. In our study, all dogs, including the two with degenerative changes in the pancreas, lived a normal life.

Our previous report on puppy no. 1 described the rapid progression from EM findings to the gross appearance of a completely atrophied pancreas. We noted also
that mild stage 1 changes were found in acinar cells at the age of 6 weeks.8 To check whether the stage 1 changes were fixation artifacts instead of real degenerative changes, the pancreas of 2 healthy control dogs was examined. These dogs revealed similar changes. In conclusion, the changes earlier reported to be stage 1 changes are artifacts, thereby confirming that previous evidence indicating that PAA is a congenital disease in GSDs is not reliable.

To halt the degenerative process on puppy no. 2, immunosuppressive medication was initiated. Whether the treatment was responsible for arresting the destruction process remains, however, unknown. Some dogs have been reported to stay in the subclinical phase of EPI for Exocrine Pancreatic Insufficiency 451
years, or sometimes for life, without treatment.9 Currently, no treatment is recommended when dogs with partial PAA have no clinical signs.9

The other 4 siblings showed neither clinical signs typical of EPI nor degenerative or inflammatory changes in the pancreas. During their lifetime a pancreatic biopsy
was taken by laparotomy 4 times, and the pancreas was also examined at necropsy.

To take serial biopsies from pancreas was the only reliable way to gain information about the pathological processes involved with the early stages of PAA before
the clinical signs of EPI appear. The 1st biopsies were taken after the weaning of the puppies to find out if EPI is a congenital disease. In an earlier study it was shown
that in about every 2nd EPI dog the clinical signs appear before 2 years of age.1 This is why we took almost all the biopsies during the 1st 2 years. During the study, the recovery from biopsy samplings was uneventful and no complications were detected.

Measurement of serum TLI is the most commonly used test of pancreatic function, being both a sensitive and practical method for detecting severe EPI. We have reported that repeatedly low serum TLI values (o5.2 mg/L) in clinically healthy dogs can be a valuable marker of subclinical EPI and suggestive of partial PAA in GSDs.10 The results of puppy no. 2 are in agreement with this conclusion. During the last 6 years of its life the serum (TLI value was constantly low, fluctuating between subnormal (2.5–5.2 mg/L) and abnormally low (o2.5 mg/L). However, we have also concluded that diagnosing partial PAA may be problematic with an indirect pancreatic function test because of overlapping results in normal and partially affected dogs.10 This was also seen in these puppies, as each of the 4 healthy puppies had on at least some occasion subnormal serum TLI values.

Our findings revealed that PAA is not a congenital disease in GSDs, and in this canine family PAA was not inherited by a simple autosomal recessive fashion of a
single gene. The study also showed that the atrophic process can destroy the entire exocrine part of the pancreas in a very short time, but the process can be halted, remaining in this position for the rest of the dog’s life. The function test helped to detect the stage of the exocrine pancreas, but it was not completely reliable.

From the Department of Equine and Small Animal Medicine (Westermarck, Wiberg) and the  Department of Basic Veterinary Sciences (Saari), Faculty of Veterinary Medicine, University of Helsinki, Helsinki, Finland. Data for one of the dogs have previously been published in Am J Vet Res 1993;54:1088-1094. Corresponding author: Elias Westermarck, Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, P.O. Box 57, 00014 Helsinki, Finland; e-mail: lias.westermarck@helsinki.fi.
Submitted June 2, 2009; Revised September 3, 2009; Accepted
November 18, 2009.
Copyright r 2010 by the American College of Veterinary Internal
Medicine
10.1111/j.1939-1676.2009.0461.x
 

Footnotes
a Viokase V, Fort Dodge Laboratories, Fort Dodge, IA
b Tylan, Elanco, Geneva, Switzerland
c Prednisolon, Leiras, Tammisaari, Finland
d Azamun, Leiras

References
1. Westermarck E, Wiberg M. Exocrine pancreatic insufficiency in dogs. Vet Clin Small Anim 2003;33:1165–1179.
2. Wiberg ME, Saari SAM, Westermarck E. Exocrine pancreatic atrophy in German Shepherd Dogs and rough-coated Collies: An end result of lymphocytic pancreatitis. Vet Pathol 1999;36:530–541.
3. Weber W, Freudiger U. Erbanalytische Untersuchungen uber die chronisce exocrine Pankreasinsuffizienz beim Deutshen Scha¨ ferhund.Schweiz Arch Tierheilkd 1977;119:257–263.
4. Westermarck E. Hereditary nature of canine pancreatic degenerative atrophy in the German Shepherd Dog. Acta Vet Scand 1980;21:389–394.
5. Moeller ME, Steiner JM, Clark LA, et al. Inheritance of pancreatic acinar atrophy in German Shepherd Dogs. Am J Vet Res 2002;10:1429–1434.
6. Clark LA, Wahl JM, Steiner JM, et al. Linkage analysis and gene expression profile of pancreatic acinar atrophy in the German Shepherd Dog. Mammalian Genome 2005;16:955–962.
7. Williams DA, Batt RM. Sensitivity and specificity of radioimmunoassay of serum trypsin-like immunoreactivity for the diagnosis of canine exocrine pancreatic insufficiency. J Am Vet Med Assoc 1988;192:195–200.
8. Westermarck E, Batt RM, Vaillant C, Wiberg M. Sequential study of pancreatic structure and function during development of panreatic acinar atrophy in German Shepherd Dog. Am J Vet Res 1993a;54:1088–1094.
9. Wiberg ME, Westermarck E. Subclinical exocrine pancreatic insufficiency in dogs. J Am Vet Med Assoc 2002;220:1183–1187.
10. Wiberg ME, Nurmi AK, Westermarck E. Serum trypsin like immunoreactivity measurement for the diagnosis of subclinical exocrine pancreatic insufficiency. J Vet Intern Med 1999;13:426–432.452 Westermarck et al

2005 – EPI Gene Expression Research

 2005 Dec;16(12):955-62. Epub 2005 Dec 8.

Linkage analysis and gene expression profile of pancreatic acinar atrophy in the German Shepherd Dog.

 

Abstract

Pancreatic acinar atrophy (PAA) is a degenerative disease of the exocrine pancreas and is the most common cause of exocrine pancreatic insufficiency in the German Shepherd Dog. Analyses of inheritance have shown that a single gene segregating in an autosomal recessive fashion is causative for PAA. To date the gene and causative mutation have not been determined. To identify a region of interest and/or candidate genes, we conducted linkage and gene expression studies. Analysis of 384 microsatellite markers resulted in a maximum two-point LOD score of 2.5 for FH2107 on CFA03. We used an oligonucleotide array to generate gene expression profiles for normal and affected pancreata. It revealed 244 genes with greater than two-fold difference in expression levels. Five genes of interest were further assessed by TaqMan quantitative real-time RT-PCR that confirmed trends observed using the microarray. One gene, gp25L, located on CFA03, was found to be downregulated by more than 500-fold in affected pancreata and was further investigated as a candidate gene. Sequence data did not reveal a mutation in the coding sequence that segregates with PAA.

PMID:
16341675
DOI:
10.1007/s00335-005-0076-1
[Indexed for MEDLINE]

2003 –  EPI Response to Long-term Enzyme Replacement

http://ethesis.helsinki.fi/julkaisut/ela/kliin/vk/wiberg/pancreat.pdf

Department of Clinical Veterinary Sciences, Section of Medicine
Faculty of Veterinary Medicine
University of Helsinki, Finland

Department of Bacteriology and Immunology
Haartman Institute
University of Helsinki, Finland
Pancreatic acinar atrophy in German shepherd dogs and rough-coated Collies
Etiopathogenesis and response to long-term enzyme replacement treatment

Maria Wiberg
Academic dissertation
To be presented, with the permission of the Faculty of Veterinary Medicine,
University of Helsinki, for public criticism in Auditorium Maxium, Hämeentie 57, Helsinki
On the 31st of January 2003 at 12 noon.
HELSINKI 2003

Supervised by: Elias Westermarck, DVM, PhD, professor
Department of Clinical Veterinary Sciences, Section of Medicine
Faculty of Veterinary Medicine, University of Helsinki
Seppo Meri, MD, PhD, docent
Department of Bacteriology and Immunology
Haartman Institute, University of Helsinki

Reviewed by: Kenneth W. Simpson, BVM&S, PhD, MRCVS, DipACVIM,
DipECVIM, professor
Department of Clinical Sciences, College of Veterinary Medicine
Cornell University, Ithaca, USA
David C. Twedt, DVM, DipACVIM, professor
Department of Clinical Sciences, College of Veterinary Medicine
Colorado State University, USA

Opponent: David A. Williams, MA, VetMb, PhD, MRCVS, DipACVIM, professor
Department of Small Animal Medicine and Surgery
College of Veterinary Medicine
Texas A&M University, USA