Bovine leukocyte adhesion deficiency

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The Bovine leukocyte adhesion deficiency (BLAD) (English Bovine leukocyte adhesion deficiency , abbreviated BLAD ) is an autosomal recessive disease in cattle bred Holstein Friesian . Affected animals have impaired white blood cell function, which makes them prone to infections. The disease was first described in 1983. The genetic cause of the disease, a single nucleotide polymorphism in a leukocyte adhesion molecule, was not revealed until nine years later.

root cause

Adhesion of the neutrophils to the vascular endothelium with subsequent migration from the vascular lumen.

The cause of the disease is a non-synonymous single nucleotide polymorphism (SNP, single nucleotide polymorphism ) at position 383 of the CD18 gene. The exchange of an adenine for a guanine causes the substitution of the amino acid aspartic acid for the amino acid glycine at position 128 in the adhesion molecule CD18. In homozygous carriers there is impaired expression of the β2 integrin of the leukocyte adhesion molecule in neutrophils .

As a result, the neutrophil granulocytes show impaired adhesiveness to different degrees . As a result, they can no longer adhere stably to the endothelium of the vessel wall and thus no longer migrate through the endothelium.

Since this disrupts the recruitment of neutrophils to inflammatory processes, the immunological defense of affected animals is significantly reduced. Accordingly, the animals suffer from recurrent infections and impaired wound healing.

There is a similar disease in humans, which is referred to here as leukocyte adhesion deficiency type I (LAD I). Canine leukocyte adhesion deficiency (CLAD), a disease that occurs in dogs, is used as a model disease to research causes and treatment options for affected people.

Symptoms

The symptoms appear clinically within the first few months of life. Affected calves show significantly reduced growth and often suffer from recurrent bacterial infections and have delayed wound healing. In the mouth, especially on the gums in the area of ​​the incisors, severe erosions and ulcerations of the mucous membrane as well as severe inflammation of the tooth supporting system ( periodontitis ) up to tooth loss and osteomyelitis of the jawbone develop. Chronic pneumonia or diarrhea are common. A persistent increase in the number of neutrophilic granulocytes ( neutrophilia ) in the blood can be detected in the laboratory .

Despite symptomatic therapy, the disease is fatal within the first two years of life, with the animals usually dying from complications of respiratory infections or diarrhea.

Inheritance

Bovine leukocyte adhesion deficiency is an autosomal recessive inheritance . Only homozygous animals develop the fatal disease, while heterozygous animals show neither symptoms nor a reduction in performance. After the genetic defect was identified as the cause of the disease, it was possible to trace it back through several generations of breeding bulls to the bull Osborndale Ivanhoe (1952–1963). This was possible because the bulls still had preserved frozen semen that could be examined for the genetic defect. Osborndale Ivanhoe is considered to be the first bull to achieve international importance for Holstein-Friesian breeding through the use of artificial insemination combined with the possibility of storing sperm for a long period in liquid nitrogen. Many of his male offspring were outstanding breeding bulls that were used intensively in Holstein breeding internationally. In particular, his son Penstate Ivanhoe Star and grandson Carlin-M Ivanhoe Bell, who were used as insemination bulls in high international demand in the 1980s and 1990s, contributed to the massive spread of the genetic defect in the Holstein-Friesian population.

Two decades after Osborndale Ivanhoe's death, the massive worldwide commitment of his offspring had resulted in a high degree of inbreeding in Holstein-Friesian breeding, which resulted in increasingly homozygous carriers. At the time the inheritance was discovered, 15% of bulls and 6% of breeding cows in the United States were carriers of the mutation.

Carriers of the BLAD allele have been identified among Holstein cattle in various countries on all five continents worldwide. The prevalence among the breeding bulls used for breeding varied.

Measures for eradication

After the inheritance was discovered, the breeding associations took measures to avoid breeding homozygous carriers and to eliminate BLAD from the Holstein population in the medium term. A genetic test was developed in the early 1990s to identify heterozygous BLAD carriers. In many countries, all bulls underwent a genetic test to determine whether they were carriers of BLAD before being used in artificial insemination. Carriers of the BLAD mutation were excluded from breeding. Already admitted bulls were marked with BL in the bull catalogs, non-carriers with FL, so that the risk of a homozygous calf could be estimated before mating.

Even if these measures have succeeded in significantly reducing the prevalence of the BLAD allele among Holstein breeding animals, it has not yet been completely eliminated.

See also

Individual evidence

  1. ↑ WA Hagemoser et al.: Granulocytopathy in a heifer. In: Jornal of the American Veterinary Medical Association. 183, 1093-1094, 1983.
  2. ↑ DE Shuster: Identification and prevalence of a genetic defect that causes leukocyte adhesion deficiency in Holstein cattle. In: Proc. Natl. Acad. Sci. UNITED STATES. Vol. 89, October 1992, pp. 9225-9229.
  3. ↑ DE Shuster: Identification and prevalence of a genetic defect that causes leukocyte adhesion deficiency in Holstein cattle. In; Proc. Natl. Acad. Sci. USA, Vol. 89, October 1992, pp. 9225-9229.
  4. ↑ TW Olchowy: Bovine leukocyte adhesion deficiency: in vitro assessment of neutrophil function and leukocyte integrin expression. In: Can J Vet Res. 58 (2), April 1994, pp. 127-133.
  5. ^ AA Schäffer, C. Klein: Animal Models of Human Granulocyte Diseases. In: Hematol Oncol Clin North Am. 27 (1), February 2013, pp. 129–148.
  6. ↑ Creevy et al .: Canine leukocyte adhesion deficiency colony for investigation of novel hematopoietic therapies. In: Vet Immunol Immunopathol. 94 (1-2), July 2003, pp. 11-22.
  7. ↑ A. Treviranus: Clinical findings and parentage of calves and young cattle with bovine leukocyte adhesion deficiency BLAD. Dissertation at the TiHo Hannover, 1993.
  8. ^ MR Ackermann: Alimentary and respiratory tract lesions in eight medically fragile Holstein cattle with bovine leukocyte adhesion deficiency (BLAD). In: Vet Pathol. 33 (3) May 1996, pp. 273-281.
  9. ^ ME Kehrli: Molecular definition of the bovine granulocytopathy syndrome: identification of deficiency of the Mac-1 (CDllWCD18) glycoprotein. In: Am J Vet Res. 51 (11) 1990, pp. 1826-1836.
  10. ↑ DE Shuster: Identification and prevalence of a genetic defect that causes leukocyte adhesion deficiency in Holstein cattle. In: Proc. Natl. Acad. Sci. UNITED STATES. Vol. 89, October 1992, pp. 9225-9229.
  11. ↑ DE Shuster: Identification and prevalence of a genetic defect that causes leukocyte adhesion deficiency in Holstein cattle. In: Proc. Natl. Acad. Sci. USA, Vol. 89, October 1992, pp. 9225-9229.
  12. ↑ H. Nagahata: Bovine leukocyte adhesion deficiency (BLAD): a review. In: J Vet Med Sci. December 2004, pp. 1475-1482.
  13. ^ MH Mirck et al.: Optimization of the PCR test for the mutation causing bovine leukocyte adhesion deficiency. Cell Mol Biol 41 (5), July 1995, pp. 695-698.
  14. ↑ DE Illie include: Control Strategies for Prevention of Undesirable Traits in Cattle - Review. Animal Science and Biotechnologies, 44 (1) 2011, pp. 415-419.
  15. ^ Holstein Foundation: Understanding Genetics and the Sire Summaries. P. 7.
  16. ↑ DE Illie include: Control Strategies for Prevention of Undesirable Traits in Cattle - Review. In: Animal Science and Biotechnologies. 44 (1) 2011, pp. 415-419.