OMIA:000438-9615 : Haemophilia B in Canis lupus familiaris (dog)

In other species: domestic cat , horse , pig

Categories: Haematopoietic system phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 306900 (trait) , 300746 (gene)

Links to relevant human diseases in MONDO:

Mendelian trait/disorder: yes

Mode of inheritance: X-linked recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 1989

Cross-species summary: Also called hemophilia B, factor IX deficiency or Christmas disease. This is one of the two X-linked bleeding disorders, haemophilia A being the other. The fact that these two disorders are X-linked in all species reported to date provides strong support for Ohno's suggestion that the X chromosome has been highly conserved throughout evolution.

Species-specific symbol: F9

History: The first reports of this disorder in dogs were on a family of Cairn Terriers diagnosed at the Ontario Veterinary College, Guelph, by Mustard et al. (1960) and Rowsell et al. (1960). The Chapel Hill colony of haemophilia B dogs was established in 1966 from the Guelph animals or their descendants (Sabatino et al., 2012). A colony of Lhasa Apso dogs - the Auburn colony - was first reported by Mauser et al. (1996). Haemophilia B was the first canine disorder to be characterised at the DNA level.

Mapping: From the results of planned matings, Brinkhous et al. (1973) showed that although the genes for both haemophilia A and haemophilia B are on the X chromosome, they are inherited independently. A similar situation exists in human.

Molecular basis: The causative mutation for this disorder was discovered via the candidate gene approach, by Evans et al. (1989), who reported that the mutant allele in the Chapel Hill Cairn Terrier colony is c.1477G>A, resulting in the substitution of glutamic acid for glycine at codon 379 in the factor-IX peptide. This particular site has been highly conserved throughout evolution: there is a glycine at this position in factor IX from human, pig and cattle. Not surprisingly, therefore, this single amino-acid substitution profoundly alters the tertiary structure of the factor-IX molecule, to the extent that no functional factor IX can be detected, which is unusual for a missense mutation . In contrast, a different mutation causes the same disorder in Lhaso Apso dogs: Mauser et al. (1996) reported a deletion of bases 772-776 plus a C>T transition at base 777 in the Auburn colony. In an affected Labrador Retriever, Brooks et al. (1997) reported a deletion of the entire gene. Gu et al. (1999) reported two new mutations - an insertionin exon 8 and another deletion. Brooks et al. (2003) reported a 1.5kb LINE1 insertion in exon 5 associated with a mild form of the disorder. In Rhodesian Ridgebacks, Mischke et al. (2011) reported "a G-A missense mutation in exon 7. This mutation results in a glycine (GGA) to glutamic acid (GAA) exchange [G244E] in the catalytic domain of the haemophilic factor IX" Brenig et al. (2019) reported a mild form of Haemophilia B in a family of Hovawarts, likely caused by "a single nucleotide deletion in the F9 promoter. . . . The deletion is located 73 bp upstream of the F9 start codon in the conserved overlapping DNA binding sites of hepatocyte nuclear factor 4α and androgen receptor." Kuder et al. (2021) described a likely causal variant in the Newfoundland breed: "a single nucleotide insertion resulting in a frameshift in the last exon (NM_001003323.2:c.821_822insA), predicted to result in a premature stop codon (NP_001003323.1:p.Asn274LysfsTer23) with a loss of 178 of 459 amino acids . . . Both the purebred Newfoundland dam and her sister were heterozygous for the insertion. Five additional male offspring developed severe hemorrhage and were hemizygous for the F9 variant and/or had a prolonged aPTT. In contrast, other male littermates had normal aPTTs and no evidence of bleeding."

Clinical features: Haemophilia B is characterised by frequent and spontaneous bleeding into joints, muscles, and body cavities, such as the chest and abdomen, due to a deficiency in factor IX (FIX, F9) (Nichols et al., 2020). This can eventually lead to arthropathy associated with progressive cartilage damage, chronic pain, lameness, and eventually joint destruction (Nichols et al., 2020). Prolonged bleeding from minor wounds and haemorrhagic complications post-surgery may also be observed (Nichols et al., 2010). Disease can be classified into mild, moderate, or severe based on plasma FIX levels with 60-70% of patients having a moderate or severe form (Nichols et al., 2020). Animals with the severe form (<1% coagulation activity) can have bleeding episodes that are life threatening. Most carriers have a reduced FIX activity of 40-60% but do not exhibit spontaneous bleeding (Nakata et al., 2006). IT thanks DVM student Ruby Xu, who provided the basis of this contribution in May 2023.

Breeds: Airedale Terrier (Dog) (VBO_0200008), Alaskan Malamute (Dog) (VBO_0200017), American Cocker Spaniel (Dog) (VBO_0200038), American Pit Bull Terrier (Dog) (VBO_0200054), Beagle (Dog) (VBO_0200131), Bichon Frise (Dog) (VBO_0200163), Black and Tan Coonhound (Dog) (VBO_0200168), Cairn Terrier (Dog) (VBO_0200267), Chow Chow (Dog) (VBO_0200361), Doberman Pinscher (Dog) (VBO_0200442), French Bulldog (Dog) (VBO_0201455), German Shepherd Dog (Dog) (VBO_0200577), German Wirehaired Pointer (Dog) (VBO_0200602), Golden Retriever (Dog) (VBO_0200610), Hovawart (Dog) (VBO_0200674), Jack Russell Terrier (Dog) (VBO_0200724), Labrador Retriever (Dog) (VBO_0200800), Lhasa Apso (Dog) (VBO_0200824), Maltese Terrier (Dog) (VBO_0200859), Mixed Breed (Dog) (VBO_0200902), Newfoundland (Dog) (VBO_0200938), Old English Sheepdog (Dog) (VBO_0200969), Rhodesian Ridgeback (Dog) (VBO_0201135), Rottweiler (Dog) (VBO_0201143), Saint Bernard (Dog) (VBO_0201160), Scottish Terrier (Dog) (VBO_0201198), Sealyham Terrier (Dog) (VBO_0201200), Shih Tzu (Dog) (VBO_0201223), Weimaraner (Dog) (VBO_0201401), Wire Fox Terrier (Dog) (VBO_0201424).
Breeds in which the phene has been documented. (If a likely causal variant has been documented for the phene, see the variant table breeds in which the variant has been reported).

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
F9 coagulation factor IX Canis lupus familiaris X NC_051843.1 (111487863..111520319) F9 Homologene, Ensembl , NCBI gene


By default, variants are sorted chronologically by year of publication, to provide a historical perspective. Readers can re-sort on any column by clicking on the column header. Click it again to sort in a descending order. To create a multiple-field sort, hold down Shift while clicking on the second, third etc relevant column headers.

WARNING! Inclusion of a variant in this table does not automatically mean that it should be used for DNA testing. Anyone contemplating the use of any of these variants for DNA testing should examine critically the relevant evidence (especially in breeds other than the breed in which the variant was first described). If it is decided to proceed, the location and orientation of the variant sequence should be checked very carefully.

Since October 2021, OMIA includes a semiautomated lift-over pipeline to facilitate updates of genomic positions to a recent reference genome position. These changes to genomic positions are not always reflected in the ‘acknowledgements’ or ‘verbal description’ fields in this table.

OMIA Variant ID Breed(s) Variant Phenotype Gene Allele Type of Variant Source of Genetic Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Year Published PubMed ID(s) Acknowledgements
636 Labrador Retriever (Dog) Haemophilia B F9 deletion, gross (>20) Naturally occurring variant X a deletion of the entire gene 1997 9394892
637 American Pit Bull Terrier (Dog) Haemophilia B F9 deletion, gross (>20) Naturally occurring variant X Gu et al. (1999): "A large deletion mutation was found in 1 breed variant, spanning the entire 5' region of the factor IX gene extending to exon 6". 1999 10544912 Following Table 3 from Kuder et al. (2021), the breed for this variant has been changed to Pit Bull Terrier. (18th October 2021)
1039 Hovawart (Dog) Haemophilia B F9 regulatory Naturally occurring variant CanFam3.1 X g.109501492del c.-73del NM_001003323.2; Brenig et al. (2019): NC_006621.3:g.109501492delC; "The deletion is located 73 bp upstream of the F9 start codon in the conserved overlapping DNA binding sites of hepatocyte nuclear factor 4alpha and androgen receptor." 2019 30846504
705 German Wirehaired Pointer (Dog) Haemophilia B F9 insertion, gross (>20) Naturally occurring variant CanFam3.1 X g.109521130_109521131insN[(1500)] NM_001003323.2; published as "insert consists of a 5' truncated canine Line-1 followed by an approximately 200-bp 3' poly (A) tract, flanked by a 15-bp direct repeat"; g. coordinate of insertion obtained from Brenig et al. (2019) 2003 14722728 CanFam3.1 coordinates copied from Table 3 of Kuder et al. (2021) (18 Oct 2021)
467 Lhasa Apso (Dog) Haemophilia B F9 deletion, small (<=20) Naturally occurring variant CanFam3.1 X g.109521356_109521361delinsT c.548_553delinsT p.(R183Lfs*3) NM_001003323.2; NP_001003323.1; published as "a deletion including nucleotides 772-776 and a C-->T transition at nucleotide 777", coordinates in the table have been updated to a recent reference genome and / or transcript and to HGVS nomenclature 1996 8896410 CanFam3.1 coordinates copied from Table 3 of Kuder et al. (2021) (18 Oct 2021)
47 Rhodesian Ridgeback (Dog) Haemophilia B F9 missense Naturally occurring variant CanFam3.1 X g.109530868G>A c.731G>A p.(G244E) NM_001003323.2; NP_001003323.1; published as p.(G244E) by Mischke et al. (2011), g. and p. coordinates were copied on the 18th October 2021 from Table 3 of Kuder et al. (2021) (relating to NP_001003323.1 ) as g.109530847G>A and p.(G237E). These g. and p. positions were incorrect. After review of Figure 1 published by Mischke et al. (2011) it was confirmed that the published p. coordinates are consistent with NM_001003323.2:c.731G>A and NP_001003323.1:p.(G244E). The g. coordinates have been updated to a recent reference genome (5th April 2022) 2011 20303304 Thank you to Agustín Arasanz for identifying that the coordinates published by Kuder et al. (2021) were inconsistent with the originally published information by Mischke et al. (2011) (5th April 2022).
1363 Newfoundland (Dog) Haemophilia B F9 insertion, small (<=20) Naturally occurring variant CanFam3.1 X g.109531586_109531587insA c.821_822insA p.(N274Kfs*23) NM_001003323.2; NP_001003323.1 2021 34680886
704 Airedale Terrier (Dog) Haemophilia B F9 insertion, gross (>20) Naturally occurring variant CanFam3.1 X g.109532012_109532013insN[(5000)] c.1247_1248insN[(5000)] NM_001003323.2; Gu et al. (1999): "An approximately 5 kb insertion disrupted exon 8 ... associated with alternative splicing between a donor site 5' and acceptor site 3' to the normal exon 8 splice junction, with introduction of a new stop codon. The resultant transcript lacked most of the factor IX catalytic domain and 3' untranslated region." 1999 10544912 CanFam3.1 coordinates copied from Table 3 of Kuder et al. (2021) (18 Oct 2021)
46 Cairn Terrier (Dog) Haemophilia B F9 missense Naturally occurring variant CanFam3.1 X g.109532018G>A c.1253G>A p.(G418E) NM_001003323.2; NP_001003323.1, published as p.(G379E) by Evans et al. (1989), coordinates in the table have been updated to a recent reference genome and / or transcript 1989 2481310 c. and p. coordinates updated from Kuder et al. (2021)

Cite this entry

Nicholas, F. W., Tammen, I., & Sydney Informatics Hub. (2024). OMIA:000438-9615: Online Mendelian Inheritance in Animals (OMIA) [dataset].


Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.

2024 Doshi, B.S., Samelson-Jones, B.J., Nichols, T.C., Merricks, E.P., Siner, J.L., French, R.A., Lee, B.J., Arruda, V.R., Callan, M.B. :
AAV gene therapy in companion dogs with severe hemophilia: Real-world long-term data on immunogenicity, efficacy, and quality of life. Mol Ther Methods Clin Dev 32:101205, 2024. Pubmed reference: 38374963. DOI: 10.1016/j.omtm.2024.101205.
2021 Arruda, V.R., Weber, J., Samelson-Jones, B.J. :
Gene therapy for inherited bleeding disorders. Semin Thromb Hemost 47:161-173, 2021. Pubmed reference: 33636747. DOI: 10.1055/s-0041-1722862.
Kuder, H., Sandzhieva-Vuzzo, L., Kehl, A., Rappaport, J.M., Müller, E., Giger, U. :
A single base insertion in F9 causing hemophilia B in a family of Newfoundland-Parti standard poodle hybrid dogs. Genes (Basel) 12:1491, 2021. Pubmed reference: 34680886. DOI: 10.3390/genes12101491.
Srinivasan, A., Herzog, R.W., Khan, I., Sherman, A., Bertolini, T., Wynn, T., Daniell, H. :
Preclinical development of plant-based oral immune modulatory therapy for haemophilia B. Plant Biotechnol J 19:1952-1966, 2021. Pubmed reference: 33949086. DOI: 10.1111/pbi.13608.
2020 Nichols, T.C., Levy, H., Merricks, E.P., Raymer, R.A., Lee, M.L. :
Preclinical evaluation of a next-generation, subcutaneously administered, coagulation factor IX variant, dalcinonacog alfa. PLoS One 15:e0240896, 2020. Pubmed reference: 33112889. DOI: 10.1371/journal.pone.0240896.
Switonski, M. :
Impact of gene therapy for canine monogenic diseases on the progress of preclinical studies. J Appl Genet 61:179-186, 2020. Pubmed reference: 32189222. DOI: 10.1007/s13353-020-00554-8.
2019 Brenig, B., Steingräber, L., Shan, S., Xu, F., Hirschfeld, M., Andag, R., Spengeler, M., Dietschi, E., Mischke, R., Leeb, T. :
Christmas disease in a Hovawart family resembling human hemophilia B Leyden is caused by a single nucleotide deletion in a highly conserved transcription factor binding site of the F9 gene promoter. Haematologica 104:2307-2313, 2019. Pubmed reference: 30846504. DOI: 10.3324/haematol.2018.215426.
2018 French, R.A., Samelson-Jones, B.J., Niemeyer, G.P., Lothrop, C.D., Merricks, E.P., Nichols, T.C., Arruda, V.R. :
Complete correction of hemophilia B phenotype by FIX-Padua skeletal muscle gene therapy in an inhibitor-prone dog model. Blood Adv 2:505-508, 2018. Pubmed reference: 29500218. DOI: 10.1182/bloodadvances.2017015313.
Gao, J., Bergmann, T., Zhang, W., Schiwon, M., Ehrke-Schulz, E., Ehrhardt, A. :
Viral Vector-Based Delivery of CRISPR/Cas9 and Donor DNA for Homology-Directed Repair in an In Vitro Model for Canine Hemophilia B. Mol Ther Nucleic Acids 14:364-376, 2018. Pubmed reference: 30690229. DOI: 10.1016/j.omtn.2018.12.008.
2016 Nichols, T.C., Hough, C., Agersø, H., Ezban, M., Lillicrap, D. :
Canine models of inherited bleeding disorders in the development of coagulation assays, novel protein replacement and gene therapies. J Thromb Haemost 14:894-905, 2016. Pubmed reference: 26924758. DOI: 10.1111/jth.13301.
2015 Cantore, A., Ranzani, M., Bartholomae, C.C., Volpin, M., Valle, P.D., Sanvito, F., Sergi, L.S., Gallina, P., Benedicenti, F., Bellinger, D., Raymer, R., Merricks, E., Bellintani, F., Martin, S., Doglioni, C., D'Angelo, A., VandenDriessche, T., Chuah, M.K., Schmidt, M., Nichols, T., Montini, E., Naldini, L. :
Liver-directed lentiviral gene therapy in a dog model of hemophilia B. Sci Transl Med 7:277ra28, 2015. Pubmed reference: 25739762. DOI: 10.1126/scitranslmed.aaa1405.
Crudele, J.M., Finn, J.D., Siner, J.I., Martin, N.B., Niemeyer, G.P., Zhou, S., Mingozzi, F., Lothrop, C.D., Arruda, V.R. :
AAV liver expression of FIX-Padua prevents and eradicates FIX inhibitor without increasing thrombogenicity in hemophilia B dogs and mice. Blood 125:1553-61, 2015. Pubmed reference: 25568350. DOI: 10.1182/blood-2014-07-588194.
Dolgin, E. :
Oral solutions. Sci Am 312:S12-3, 2015. Pubmed reference: 25597119.
Koeberl, D.D. :
A natural choice for hemophilia B. Blood 125:1509-10, 2015. Pubmed reference: 25745178. DOI: 10.1182/blood-2015-01-622506.
Nichols, T.C., Whitford, M.H., Arruda, V.R., Stedman, H.H., Kay, M.A., High, K.A. :
Translational data from adeno-associated virus-mediated gene therapy of hemophilia B in dogs. Hum Gene Ther Clin Dev 26:5-14, 2015. Pubmed reference: 25675273. DOI: 10.1089/humc.2014.153.
Sohn, E. :
Dogged pursuit. Sci Am 312:S18-9, 2015. Pubmed reference: 25597122.
2014 Nichols, T., Whitford, M.H., Arruda, V.R., Stedman, H.H., Kay, M.A., High, K.A. :
Translational data from AAV-mediated gene therapy of hemophilia B in dogs. Hum Gene Ther Clin Dev , 2014. Pubmed reference: 25548971. DOI: 10.1089/hum.2014.153.
Sherman, A., Schlachterman, A., Cooper, M., Merricks, E.P., Raymer, R.A., Bellinger, D.A., Herzog, R.W., Nichols, T.C. :
Portal vein delivery of viral vectors for gene therapy for hemophilia. Methods Mol Biol 1114:413-26, 2014. Pubmed reference: 24557919. DOI: 10.1007/978-1-62703-761-7_27.
2012 Barr, J.W., McMichael, M. :
Inherited disorders of hemostasis in dogs and cats. Top Companion Anim Med 27:53-8, 2012. Pubmed reference: 23031456. DOI: 10.1053/j.tcam.2012.07.006.
Finn, J.D., Nichols, T.C., Svoronos, N., Merricks, E.P., Bellenger, D.A., Zhou, S., Simioni, P., High, K.A., Arruda, V.R. :
The efficacy and the risk of immunogenicity of FIX Padua (R338L) in hemophilia B dogs treated by AAV muscle gene therapy. Blood 120:4521-3, 2012. Pubmed reference: 22919027. DOI: 10.1182/blood-2012-06-440123.
Mischke, R. :
[Haemophilia A and B in dogs]. Tierarztl Prax Ausg K Kleintiere Heimtiere 40:44-53; quiz 54, 2012. Pubmed reference: 22331328.
Nichols, T.C., Franck, H.W., Franck, C.T., De Friess, N., Raymer, R.A., Merricks, E.P. :
Sensitivity of whole blood clotting time and activated partial thromboplastin time for factor IX: relevance to gene therapy and determination of post-transfusion elimination time of canine factor IX in hemophilia B dogs. J Thromb Haemost 10:474-6, 2012. Pubmed reference: 22482117.
Nolte, M.W., Nichols, T.C., Mueller-Cohrs, J., Merricks, E.P., Pragst, I., Zollner, S., Dickneite, G. :
Improved kinetics of rIX-FP, a recombinant fusion protein linking factor IX with albumin, in cynomolgus monkeys and hemophilia B dogs. J Thromb Haemost 10:1591-9, 2012. Pubmed reference: 22726310. DOI: 10.1111/j.1538-7836.2012.04826.x.
Sabatino, D.E., Nichols, T.C., Merricks, E., Bellinger, D.A., Herzog, R.W., Monahan, P.E. :
Animal models of hemophilia. Prog Mol Biol Transl Sci 105:151-209, 2012. Pubmed reference: 22137432. DOI: 10.1016/B978-0-12-394596-9.00006-8.
2011 Fischer, T.H., Nichols, T.C., Scull, C.M., Smith, C.J., Demcheva, M. :
Poly-N-acetylglucosamine fibers amplify the effectiveness of recombinant factor VIIA on clot formation in hemophilia B canine blood. J Trauma 71:S171-5, 2011. Pubmed reference: 21814114. DOI: 10.1097/TA.0b013e31822556f4.
Kim, J., Noh, D., Song, R., Lee, D., Cho, H., Yu, D., Park, J., Park, C. :
Hemophilia B (factor IX deficiency) in a Labrador retriever dog. Korean Journal of Veterinary Service 23:191-193, 2011. URL:
Mischke, R., Kühnlein, P., Kehl, A., Langbein-Detsch, I., Steudle, F., Schmid, A., Dandekar, T., Czwalinna, A., Müller, E. :
G244E in the canine factor IX gene leads to severe haemophilia B in Rhodesian Ridgebacks. Vet J 187:113-8, 2011. Pubmed reference: 20303304. DOI: 10.1016/j.tvjl.2010.01.017.
2010 Nichols, T.C., Raymer, R.A., Franck, H.W., Merricks, E.P., Bellinger, D.A., DeFriess, N., Margaritis, P., Arruda, V.R., Kay, M.A., High, K.A. :
Prevention of spontaneous bleeding in dogs with haemophilia A and haemophilia B. Haemophilia :19-23, 2010. Pubmed reference: 20586797. DOI: 10.1111/j.1365-2516.2010.02255.x.
2009 Nichols, TC., Dillow, AM., Franck, HW., Merricks, EP., Raymer, RA., Bellinger, DA., Arruda, VR., High, KA. :
Protein replacement therapy and gene transfer in canine models of hemophilia A, hemophilia B, von willebrand disease, and factor VII deficiency. ILAR J 50:144-67, 2009. Pubmed reference: 19293459.
2006 Nakata, M., Sakai, M., Sakai, T. :
Hemophilia B in a crossbred Maltese dog. J Vet Med Sci 68:1223-4, 2006. Pubmed reference: 17146185. DOI: 10.1292/jvms.68.1223.
2005 Wang, L., Calcedo, R., Nichols, TC., Bellinger, DA., Dillow, A., Verma, IM., Wilson, JM. :
Sustained correction of disease in naive and AAV2-pretreated hemophilia B dogs: AAV2/8-mediated, liver-directed gene therapy. Blood 105:3079-86, 2005. Pubmed reference: 15637142. DOI: 10.1182/blood-2004-10-3867.
2003 Brooks, MB., Gu, W., Barnas, JL., Ray, J., Ray, K. :
A Line 1 insertion in the Factor IX gene segregates with mild hemophilia B in dogs. Mamm Genome 14:788-95, 2003. Pubmed reference: 14722728. DOI: 10.1007/s00335-003-2290-z.
Ehrhardt, A., Xu, H., Dillow, A.M., Bellinger, D.A., Nichols, T.C., Kay, M.A. :
A gene-deleted adenoviral vector results in phenotypic correction of canine hemophilia B without liver toxicity or thrombocytopenia Blood 102:2403-11, 2003. Pubmed reference: 12805062. DOI: 10.1182/blood-2003-01-0314.
2002 Mount, J.D., Herzog, R.W., Tillson, D.M., Goodman, S.A., Robinson, N., McCleland, M.L., Bellinger, D., Nichols, T.C., Arruda, V.R., Lothrop, C.D., High, K.A. :
Sustained phenotypic correction of hemophilia B dogs with a factor IX null mutation by liver-directed gene therapy Blood 99:2670-2676, 2002. Pubmed reference: 11929752.
2001 Herzog, R.W., Mount, J.D., Arruda, V.R., High, K.A., Lothrop, C.D. :
Muscle-directed gene transfer and transient immune suppression result in sustained partial correction of canine hemophilia B caused by a null mutation Molecular Therapy: the Journal of the American Society of Gene Therapy 4:192-200, 2001. Pubmed reference: 11545609. DOI: 10.1006/mthe.2001.0442.
2000 Herzog, R.W., Arruda, V.R., Fisher, T.H., Read, M.S., Nichols, T.C., High, K.A. :
Absence of circulating factor IX antigen in hemophilia B dogs of the UNC-Chapel Hill colony. Thromb Haemost 84:352-4, 2000. Pubmed reference: 10959714.
Mischke, R. :
Influence of factor VIII : C and factor IX activity in plasmas of haemophilic dogs on the activated partial thromboplastin time measured with two commercial reagents Haemophilia 6:135-139, 2000. Pubmed reference: 10792470.
Mischke, R. :
Sensitivity of the reaction time of the resonance thrombogram for factor VIII : C and factor IX deficiencies in the blood of dogs with haemophilia A or B Haemophilia 6:575-580, 2000. Pubmed reference: 11012705.
Wang, L.L., Nichols, T.C., Read, M.S., Bellinger, D.A., Verma, I.M. :
Sustained expression of therapeutic level of factor IX in hemophilia B dogs by AAV-mediated gene therapy in liver Molecular Therapy: the Journal of the American Society of Gene Therapy 1:154-158, 2000. Pubmed reference: 10933925. DOI: 10.1006/mthe.2000.0031.
1999 Brooks, M. :
A review of canine inherited bleeding disorders: Biochemical and molecular strategies for disease characterization and carrier detection Journal of Heredity 90:112-118, 1999. Pubmed reference: 9987916.
Chao, H., Samulski, R.J., Bellinger, D.A., Monahan, P.E., Nichols, T.C., Walsh, C.E. :
Persistent expression of canine factor IX in hemophilia B canines Gene Therapy 6:1695-1704, 1999. Pubmed reference: 10516718. DOI: 10.1038/
Chao, H., Walsh, C.E. :
Endogenous canine FIX antigen exists in Chapel Hill strain hemophilia B canine. Thromb Haemost 82:1378, 1999. Pubmed reference: 10544943.
Gu, W., Brooks, M., Catalfamo, J., Ray, J., Ray, K. :
Two distinct mutations cause severe hemophilia B in two unrelated canine pedigrees. Thromb Haemost 82:1270-5, 1999. Pubmed reference: 10544912.
Herzog, R.W., Yang, E.Y., Couto, L.B., Hagstrom, J.N., Elwell, D., Fields, P.A., Burton, M., Bellinger, D.A., Read, M.S., Brinkhous, K.M., Podsakoff, G.M., Nichols, T.C., Kurtzman, G.J., High, K.A. :
Long-term correction of canine hemophilia B by gene transfer of blood coagulation factor IX mediated by adeno-associated viral vector Nature Medicine 5:56-63, 1999. Pubmed reference: 9883840. DOI: 10.1038/4743.
Snyder, R.O., Miao, C., Meuse, L., Tubb, J., Donahue, B.A., Lin, H.F., Stafford, D.W., Patel, S., Thompson, A.R., Nichols, T., Read, M.S., Bellinger, D.A., Brinkhous, K.M., Kay, M.A. :
Correction of hemophilia B in canine and murine models using recombinant adeno-associated viral vectors Nature Medicine 5:64-70, 1999. Pubmed reference: 9883841. DOI: 10.1038/4751.
1998 Monahan, P.E., Samulski, R.J., Tazelaar, J., Xiao, X., Nichols, T.C., Bellinger, D.A., Read, M.S., Walsh, C.E. :
Direct intramuscular injection with recombinant aav vectors results in sustained expression in a dog model of hemophilia Gene Therapy 5:40-49, 1998. Pubmed reference: 9536263. DOI: 10.1038/
1997 Brooks, M.B., Gu, W., Ray, K. :
Complete deletion of factor IX gene and inhibition of factor IX activity in a labrador retriever with hemophilia B. J Am Vet Med Assoc 211:1418-21, 1997. Pubmed reference: 9394892.
Chang, J.Y., Monroe, D.M., Stafford, D.W., Brinkhous, K.M., Roberts, H.R. :
Replacing the first epidermal growth factor-like domain of factor ix with that of factor vii enhances activity in vitro and in canine hemophilia b Journal of Clinical Investigation 100:886-892, 1997. Pubmed reference: 9259588. DOI: 10.1172/JCI119604.
Gu, W.K., Ray, K. :
A polymorphic (TTTA), tandem repeat in an intron of the canine factor IX gene Animal Genetics 28:370, 1997. Pubmed reference: 9363602.
Liles, D., Landen, C.N., Monroe, D.M., Lindley, C.M., Read, M.S., Roberts, H.R., Brinkhous, K.M. :
Extravascular administration of factor ix - potential for replacement therapy of canine and human hemophilia b Thrombosis & Haemostasis 77:944-948, 1997.
1996 Brinkhous, K.M., Sigman, J.L., Read, M.S., Stewart, P.F., Mccarthy, K.P., Timony, G.A., Leppanen, S.D., Rup, B.J., Keith, J.C., Garzone, P.D., Schaub, R.G. :
Recombinant human factor IX - replacement therapy, prophylaxis, and pharmacokinetics in canine hemophilia B Blood 88:2603-2610, 1996. Pubmed reference: 8839853.
Fang, B., Wang, H., Gordon, G., Bellinger, D.A., Read, M.S., Brinkhous, K.M., Woo, S.L.C., Eisensmith, R.C. :
Lack of persistence of E1(-) recombinant adenoviral vectors containing a temperature-sensitive E2A mutation in immunocompetent mice and hemophilia B dogs Gene Therapy 3:217-222, 1996. Pubmed reference: 8646552.
Kruth, S. :
Canine models for gene therapy Transfusion Science 17:71-77, 1996.
Mauser, A.E., Whitlark, J., Whitney, K.M., Lothrop, C.D. :
A deletion mutation causes hemophilia B in Lhasa Apso dogs Blood 88:3451-3455, 1996. Pubmed reference: 8896410.
Mischke, R., Hanies, R., Deniz, A., Hart, S. :
Haemophilia B in a male mongrel dog - therapy of a haemorrhagic crisis with fresh frozen plasma [German] Deutsche Tierarztliche Wochenschrift 103:3-6, 1996. Pubmed reference: 8647012.
Sugahara, Y., Catalfamo, J., Brooks, M., Hitomi, E., Bajaj, S.P., Kurachi, K. :
Isolation and characterization of canine factor IX Thrombosis & Haemostasis 75:450-455, 1996.
1995 Feldman, D.G., Brooks, M.B., Dodds, W.J. :
Hemophilia B (factor IX deficiency) in a family of German Shepherd Dogs Journal of the American Veterinary Medical Association 206:1901-1905, 1995. Pubmed reference: 7790304.
1994 Kay, M.A., Landen, C.N., Rothenberg, S.R., Taylor, L.A., Leland, F., Wiehle, S., Fang, B.L., Bellinger, D., Finegold, M., Thompson, A.R., Read, M., Brinkhous, K.M., Woo, S.L.C. :
In Vivo Hepatic Gene Therapy - Complete Albeit Transient Correction of Factor IX Deficiency in Hemophilia B Dogs Proceedings of the National Academy of Sciences of the United States of America 91:2353-2357, 1994. Pubmed reference: 8134398.
Lozier, J.N., Thompson, A.R., Hu, P.C., Read, M., Brinkhous, K.M., High, K.A., Curiel, D.T. :
Efficient Transfection of Primary Cells in a Canine Hemophilia-B Model Using Adenovirus Polylysine DNA Complexes Human Gene Therapy 5:313-322, 1994. Pubmed reference: 8018746. DOI: 10.1089/hum.1994.5.3-313.
1993 Brooks, M., Catalfamo, J. :
Buccal mucosa bleeding time is prolonged in canine models of primary hemostatic disorders. Thrombosis and Haemostasis 70:777-780, 1993. Pubmed reference: 8128434.
Kay, M.A., Rothenberg, S., Landen, C.N., Bellinger, D.A., Leland, F., Toman, C., Finegold, M., Thompson, A.R., Read, M.S., Brinkhous, K.M., Woo, S.L.C. :
In Vivo Gene Therapy of Hemophilia-B - Sustained Partial Correction in Factor-IX-Deficient Dogs Science 262:117-119, 1993. Pubmed reference: 8211118.
Marx, J. :
A first step toward gene therapy for hemophilia B? Science 262:29-30, 1993. Pubmed reference: 8211125. DOI: 10.1126/science.8211125.
1991 Kooistra, H.S., Slappendel, R.J. :
A Young Male Mongrel with Haemophilia-B (Christmas Disease) Tijdschrift Voor Diergeneeskunde 116:281-285, 1991. Pubmed reference: 2028457.
1990 Axelrod, J.H., Read, M.S., Brinkhous, K.M., Verma, I.M. :
Phenotypic correction of factor IX deficiency in skin fibroblasts of hemophilic dogs. Proc Natl Acad Sci U S A 87:5173-7, 1990. Pubmed reference: 2367529. DOI: 10.1073/pnas.87.13.5173.
1989 Brinkhous, K.M., Hedner, U., Garris, J.B., Diness, V., Read, M.S. :
Effect of recombinant factor VIIa on the hemostatic defect in dogs with hemophilia A, hemophilia B, and von Willebrand disease. Proc Natl Acad Sci U S A 86:1382-6, 1989. Pubmed reference: 2784006.
Evans, J.P., Brinkhous, K.M., Brayer, G.D., Reisner, H.M., High, K.A. :
Canine hemophilia B resulting from a point mutation with unusual consequences. Proc Natl Acad Sci U S A 86:10095-9, 1989. Pubmed reference: 2481310. DOI: 10.1073/pnas.86.24.10095.
1988 Fogh, J.M., Fogh, I.T. :
Inherited coagulation disorders. Vet Clin North Am Small Anim Pract 18:231-43, 1988. Pubmed reference: 3282382.
1986 Littlewood, J.D., Matić, S.E., Smith, N. :
Factor IX deficiency (haemophilia B, Christmas disease) in a crossbred dog. Vet Rec 118:400-1, 1986. Pubmed reference: 3716095.
1984 Fogh, J.M., Nygaard, L., Andresen, E., Nilsson, I.M. :
Hemophilia in dogs, with special reference to hemophilia A among German shepherd dogs in Denmark. I: Pathophysiology, laboratory tests and genetics. Nord Vet Med 36:235-40, 1984. Pubmed reference: 6436787.
Verlander, J.W., Gorman, N.T., Dodds, W.J. :
Factor IX deficiency (hemophilia B) in a litter of Labrador retrievers. J Am Vet Med Assoc 185:83-4, 1984. Pubmed reference: 6746380.
1983 Campbell, K.L., Greene, C.E., Dodds, W.J. :
Factor IX deficiency (hemophilia B) in a Scottish terrier. J Am Vet Med Assoc 182:170-1, 1983. Pubmed reference: 6826437.
1980 Sherding, R.G., DiBartola, S.P. :
Hemophilia B (factor IX deficiency) in an Old English Sheepdog. J Am Vet Med Assoc 176:141-2, 1980. Pubmed reference: 7353989.
Spurling, N.W. :
Hereditary disorders of haemostasis in dogs: a critical review of the literature Veterinary Bulletin 50:151-173, 1980.
1979 Peterson, M.E., Dodds, W.J. :
Factor IX deficiency in an Alaskan Malamute. J Am Vet Med Assoc 174:1326-7, 1979. Pubmed reference: 511734.
1978 Goldsmith, J.C., Chung, K.S., Roberts, H.R. :
A simple assay for human factor IX: use of canine hemophilia B plasma as substrate. Thromb Res 12:497-502, 1978. Pubmed reference: 653637.
1975 Slappendel, R.J. :
Hemophilia A and hemophilia B in a family of French bulldogs Tijdschrift voor Diergeneeskunde 100:1075-1088, 1975. Pubmed reference: 1209580.
1974 Dodds, W.J. :
Hereditary and acquired hemorrhagic disorders in animals. Prog Hemost Thromb 2:215-47, 1974. Pubmed reference: 4604529.
Webster, W.P., Mandel, S.R., Reddick, R.L., Wagner, J.L., Penick, G.D. :
Orthotopic liver transplantation in canine hemophilia B. Am J Physiol 226:496-500, 1974. Pubmed reference: 4593805.
1973 Brinkhous, K.M., Davis, P.D., Graham, J.B., Dodds, W.J. :
Expression and linkage of genes for X-linked hemophilias A and B in the dog. Blood 41:577-85, 1973. Pubmed reference: 4688873.
1968 Davis, P.D. :
Canine double heterozygotes for hemophilia A and B. Federation Proceedings 27:627, 1968.
1964 Parks, B.J., Brinkhous, K.M., Harris, P.F., Penick, G.D. :
Laboratory detection of female carriers of canine hemophilia. Thromb Diath Haemorrh 12:368-76, 1964. Pubmed reference: 14254695.
1962 Mustard, J.F., Basser, W., Hedgardt, G., Secord, D., Rowsell,H.C., Downie, H.G. :
A comparison of the effect of serum and plasma transfusions on the clotting defect in canine haemophilia B British Journal of Haematology 8:36-42, 1962. Pubmed reference: 14477606.
1960 Mustard, J.F., Rowsell, H.C., Robinson, G.A., Hoeksema, T.D., Downie, H.G. :
Canine hemophilia B (Christmas disease) British Journal of Haematology 6:259-266, 1960. Pubmed reference: 13727144.
Rowsell, H.C., Downie, H.G., Mustard, J.F., Leeson, J.E., Archibald, J.A. :
A disorder resembling hemophilia B (Christmas disease) in dogs. J Am Vet Med Assoc 137:247-50, 1960. Pubmed reference: 14439728.

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