Clinicopathological Phenotype of Autosomal Recessive Cholesterol Deficiency in Holstein Cattle

Mock, T.; Mehinagic, K.; Menzi, F.; Studer, E.; Oevermann, A.; Stoffel, M.H.; Drögemüller, C.; Meylan, M.; Regenscheit, N.

A n inherited autosomal recessive genetic defect in Holstein calves, named cholesterol deficiency (CD), was reported for the first time in the summer of 2015 in Germany. 1, 2 Homozygous calves demonstrate clinical signs of diarrhea unresponsive to treatment and failure to thrive. 1 They suffer marked hypocholesterolemia and hypolipidemia, indicating an inherited fat metabolism disorder. These animals usually die within the first 6 months of life, and it has been assumed that about 80% of homozygous affected calves do not survive more than 1 year. 1 Heterozygous carrier animals do not show any clinical signs but have reduced levels of blood cholesterol and triglycerides. 1 Breeding organizations in Switzerland and other countries have reported an increasing occurrence of cases in Holstein cattle. The causal mutation has recently been identified in the apolipoprotein B gene (APOB). 3 A 1,299-bp insertion of a transposable element located in exon 5 of bovine APOB was shown to be perfectly associated with the disease and leads to truncated transcripts and aberrant splicing. 3 The Canadian artificial insemination Holstein sire Maughlin Storm, born in 1991, has been identified genetically to be the first carrier bull. 2 A significant recent advancement has been the development of a PCR-based direct gene test, allowing the detection of animals with CD without pedigree information. 3 In human patients, truncating mutations in APOB give rise to familial hypobetalipoproteinemia (FHBL). The APOB encodes 2 proteins via a mRNA-editing process: the APOB-48 protein is required for chylomicron production in the small intestine, and the APOB-100 protein is expressed in the liver. The APOB-100 protein is a structural component of very low-density lipoprotein (VLDL) and its metabolic products and serves as the ligand for low-density lipoprotein (LDL) receptor-mediated endocytosis of lipid particles. 4 The clinical consequences of the mutation are well described in human medicine, but have not been described to date in cattle. The aim of this report is to describe the clinical and pathological phenotype associated with the genetic defect of APOB causing this new disease entity in Holstein cattle.