This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Hemolytic transfusion reactions are significant, severe complications in human patients as well as domestic animals receiving blood. We have established a collaboration with Steven Spitalnik at Columbia University in New York to further define blood group systems in dogs and cats. Feline Blood Groups Only one blood group system has been thusfar recognized in cats. This feline AB system consists of three blood types: type A, B, and AB. A-B incompatibilities are responsible for acute hemolytic transfusion reactions and hemolysis of the newborn. Our collaborative studies have well characterized the inheritance biochemical nature and immunologic consequences over the past decade. Furthermore, we have assisted in the development and the evaluation of gel test system to detect accurately the three blood types; initial studies on a prototype are very encouraging. Gel test systems have recently becoming standard methods for blood typing in humans. In the process of examining compatibility of animals receiving blood we recently recognized a new blood group antigen. This antigen is named Mik and appears to occur very commonly, hence this may be a novel high frequency red cell antigen. We have documented the development of naturally occurring alloantibodies against this antigen in animals lacking the antigen. Further investigations are planned to better define the antigen and its involvement in hemolytic transfusion reactions. Canine Blood Groups Canine blood groups have been examined for many decades but the biochemical and molecular bases of the more than a dozen blood group systems have not been defined. This is partially due to the lack of appropriate typing reagents and their apparent unimportance at the time of a first transfusion. Nevertheless we documented the clinical importance of the Dog Erythrocyte Antigen (DEA) 1.1 and have applied the same gel test method with a monoclonal antibody to DEA 1.1 for routine screening of dogs. In the process of these studies we also recognized a Dalmatian with a pan-incompatibility to all blood donors tested. This included 50 dogs from various breeds. However, when testing this Dalmatian to other Dalmatians, 3 of 13 were found to be compatible, suggesting that they also lacked this red cell antigen. Because of the common occurrence of this antigen and its absence in some Dalmatians it was named Dal and may represent a new high frequency red cell antigen. Further investigations are planned to better define the antigen and its involvement in hemolytic transfusion rea

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Animal (Mammalian and Nonmammalian) Model, and Animal and Biological Material Resource Grants (P40)
Project #
5P40RR002512-22
Application #
7391971
Study Section
National Center for Research Resources Initial Review Group (RIRG)
Project Start
2006-08-01
Project End
2007-07-31
Budget Start
2006-08-01
Budget End
2007-07-31
Support Year
22
Fiscal Year
2006
Total Cost
$3,357
Indirect Cost
Name
University of Pennsylvania
Department
Pathology
Type
Schools of Veterinary Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
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Flanagan-Steet, Heather; Aarnio, Megan; Kwan, Brian et al. (2016) Cathepsin-Mediated Alterations in TGFß-Related Signaling Underlie Disrupted Cartilage and Bone Maturation Associated With Impaired Lysosomal Targeting. J Bone Miner Res 31:535-48
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