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Oral and Poster Abstracts

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on recent discoveries concerning the mouse mutants dan <strong>and</strong> mdig<br />

<strong>and</strong> a mouse knockout for Lrp4, we present solid evidence that the<br />

subsequent substitution in LRP4 exon 33 is a strong c<strong>and</strong>idate causal<br />

mutation for syndactyly in Holstein cattle.<br />

333 Inherited Defects of the Brown Breed: Genetic Diseases of the<br />

Central Nervous System<br />

K. Doll<br />

University of Giessen, Clinic for Ruminants <strong>and</strong> Pigs, Giessen,<br />

Germany<br />

Bovine progressive degenerative myeloencephalopathy (PDME)<br />

or weaver syndrome, an autosomal recessively inherited<br />

neurological disease, was first observed in American Brown Swiss<br />

in 1973. Clinical signs usually begin at 6 months to 2 years. The<br />

progressive bilateral hindlimb weakness <strong>and</strong> proprioceptive deficits<br />

cause difficulty in rising <strong>and</strong> a weaving, hypermetric gait, <strong>and</strong> finally<br />

recumbency.Pathological findings include axonal degeneration in<br />

the white matter of the thoracal spinal cord, <strong>and</strong> myelin degradation.<br />

Additionally nerve fibers of the peripheral nervous system exhibit<br />

comparable mitochondrial alterations <strong>and</strong> identical alterations are<br />

encountered in skeletal muscles. Weaver syndrome can be<br />

considered as a primary axonopathy, <strong>and</strong> a mitochondria-related<br />

encephalomyolo-/myopathy, respectively. Bovine spinal muscular<br />

atrophy (SMA), an inheritable autosomal recessive neurological<br />

disease, is characterized by degeneration <strong>and</strong> loss of motor neurons<br />

of the spinal cord <strong>and</strong> motor nuclei of the brain stem, <strong>and</strong><br />

denervation <strong>and</strong> neurogenic atrophy of the striated muscle. Electron<br />

microscopy reveals accumulation of neurofilaments <strong>and</strong><br />

mitochondria in affected neurons. SMA was first described in 1988<br />

in calves of the Red Danish breed x American Brown Swiss. The<br />

progressive weakness with respiratory failure finally causes death in<br />

the affected animals. The disease shares many features with<br />

Werdnig-Hoffmann disease in man <strong>and</strong> the spinal muscular<br />

atrophies of other animals. Bovine spinal dysmyelination (SDM),<br />

an autosomal recessive neurological disorder, was first reported in<br />

new-born brown Swiss x Braunvieh calves in 1993 <strong>and</strong> in calves of<br />

the Red Danish Dairy breed x American Brown Swiss (1994). It is<br />

characterized by congenital lateral recumbency, opisthotonus,<br />

extension of the limbs, normal to increased reflexes, <strong>and</strong> normal<br />

alertness. At histological examination dysmyelination occurres in<br />

spinal tracts, affecting the ascending gracile funiculus, the ascending<br />

dorsolateral spinocerebellar tract, <strong>and</strong> the mainly descending<br />

sulcomarginal tract. Deficient myelin production, loss of myelin,<br />

consecutive axonal degenerations, <strong>and</strong> astrogliosis within these<br />

tracts are the histological characteristics. This primary myelination<br />

disorder differs from other hereditary neurological diseases in<br />

Brown Swiss <strong>and</strong> Braunvieh cattle, i.e. the weaver-syndrome <strong>and</strong> the<br />

spinal muscular atrophy.<br />

334 Inherited Defects of the Brown Breed: Arachnomelia<br />

A. Gentile 1 , S. Testoni 2<br />

1<br />

University of Bologna, Veterinary Clinical Department, Bologna,<br />

Italy<br />

2<br />

University of Padova, Department of Veterinary Clinical Sciences,<br />

Padova, Italy<br />

Arachnomelia (“spider-legs”) is a congenital abnormality of the<br />

skeletal system giving the animal a spidery look, <strong>and</strong> reported both<br />

in Brown <strong>and</strong> Simmenthal calves.The most important pathologic<br />

findings are: facial deformities (i.e. brachygnatia inferior <strong>and</strong><br />

concave rounding of the dorsal profile of the maxilla), bone<br />

dolichostenomelia, angular deformities in the distal part of the hind<br />

legs, muscular atrophy <strong>and</strong> cardiac malformations. The bones of the<br />

legs appear to be more fragile than normal <strong>and</strong> spontaneous fracture<br />

during calving may injure the dam.<br />

335 Inherited Defects of the Brown Breed: Genetic Aspects<br />

C. Droegemueller<br />

University of Berne, Institute of Animal Breeding, Bern, Switzerl<strong>and</strong><br />

Four independent different genetic diseases were observed in Brown<br />

Swiss cattle. For all phenotypes an autosomal monogenic recessive<br />

inheritance has been described. In 1993 the first genetic disease in<br />

cattle, progressive degenerative myeloencephalopathy (Weaver<br />

disease), which is also associated with increased milk production,<br />

was genetically mapped to bovine chromosome 13. In 2001 the<br />

spinal dysmyelination (SDM) was mapped in crossbred American<br />

Brown Swiss cattle to bovine chromosome 11. In 2007 the first<br />

causative mutation for a genetic defect in German Brown cattle was<br />

reported for the neurodegenerative disease spinal muscular atrophy<br />

(SMA). The bovine FVT1 gene, encoding 3-ketodihydrosphingosine<br />

reductase, which catalyzes a crucial step in the glycosphingolipid<br />

metabolism, showed a perfectly SMA associated missense mutation.<br />

In 2008 a microsatellite marker based whole genome scan revealed<br />

significant linkage to markers on bovine chromosome 5 for the<br />

mutation causing arachnomelia or spider legs in Swiss <strong>and</strong> Italian<br />

Brown cattle. To select against these genetic defects either linked<br />

microsatellite markers (Weaver, SDM <strong>and</strong> arachnomelia) or the<br />

determination of the causative mutation itself (SMA) can be used to<br />

identify carriers. These molecular findings allow efficient selection<br />

against the four most frequently genetic diseases in Brown cattle.<br />

336 Bovine Leucocyte Adhesion Deficiency: History <strong>and</strong> Control.<br />

A Retrospective Survey<br />

H. Nagahata<br />

Rakuno Gakuen University, Department of Animal Health, Rakuno,<br />

Japan<br />

Bovine leucocyte adhesion deficiency (BLAD) in Holstein cattle is<br />

an autosomal recessive congenital disease characterized by recurrent<br />

bacterial infections, delayed wound healing <strong>and</strong> stunted growth, <strong>and</strong><br />

is also associated with persistent marked neutrophilia. The<br />

molecular basis of BLAD is a single point mutation (adenine to<br />

guanine) at position 383 of the CD18 gene, which caused an<br />

asparatic acid to glycine substitution at amino acid 128 (D128G) in<br />

the adhesion molecule CD18. Neutrophils from BLAD cattle have<br />

impaired expression of the beta-2 integrin (CD11a,b,c/CD18) of the<br />

leucocyte adhesion molecule. Abnormalities in a wide spectrum of<br />

adherence dependent functions of leucocytes have been<br />

characterized. Cattle affected with BLAD have severe ulcers on oral<br />

mucous membranes, severe periodontitis, loss of teeth, chronic<br />

pneumonia <strong>and</strong> recurrent or chronic diarrhea. Affected cattle die at<br />

an early age due to the infectious complications. Holstein bulls,<br />

including carrier sires that had a mutant BLAD gene in heterozygote<br />

were controlled from dairy cattle. The control of BLAD in Holstein<br />

cattle by publishing the genotypes <strong>and</strong> avoiding the mating between<br />

BLAD carriers was found to be successful. The overview of the<br />

BLAD in Holstein cattle will be presented.<br />

365 Spastic Paresis <strong>and</strong> Spastic Syndrome: a Never Ending Story<br />

A. Gentile<br />

University of Bologna, Veterinary Clinical Department, Bologna,<br />

Italy<br />

Despite the fact that Spastic Paresis <strong>and</strong> Spastic Syndrome have been<br />

known for many decades, many of their pathogenic <strong>and</strong> etiological<br />

mechanisms remain unknown. Spastic Paresis is clinically<br />

characterized by a hyperextension of the rear limbs (“straight hock”)<br />

due to a contraction of the muscles which form the Achilles tendon.<br />

Signs of Spastic Paresis appear usually at the age of 3 to 8 months.<br />

Affected animal has a stiff gait <strong>and</strong> moves without normal hock<br />

flexion. In the most severe cases the leg is held so that the foot just<br />

touches the ground with the toe or remains completely raised from<br />

the ground <strong>and</strong> extended backwards. Spastic Paresis is considered to<br />

be caused by a spastic contraction of the antigravitational, foot<br />

extensor muscle group, especially the gastrocnemius <strong>and</strong> the<br />

superficial digital flexor. The contraction of the quadriceps femoris<br />

characterizes the recently described atypical form of Spastic Paresis<br />

of the femoral quadriceps, observed firstly in Belgian White Blue<br />

calves but experienced also in Romagnola animals. The muscular<br />

spasticity should be attributed to a hyperactivity of the myotatic<br />

reflex (“stretch reflex”). The dysfunction lies primarily in the<br />

gamma-pathway. Spastic Syndrome (“crampiness”, “Krämpfigkeit”)<br />

is a chronic condition that occurs in adult cattle. It is a particular<br />

problem in mature bulls maintained in artificial insemination centres<br />

but can affect also cows in a recurrent or in a progressive form. The<br />

disease is characterized by intermittent bilateral spasm of skeletal<br />

muscles of the pelvic girdle, including the muscles of the rump. Each<br />

Genetics Diseases Workshop 331

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