X-linked anhidrotic ectodermal dysplasia in cattle is caused by a partial deletion of the bovine ED1 gene
Congenital hypotrichosis, an almost complete lack of teeth and the complete absence of eccrine nasolabial glands, was observed among the progeny of a normal cow of the black and white German Holstein breed. Similar congenital anomalies are known in humans and mice as X-linked anhidrotic ectodermal dysplasia (ED1), leading to the impaired formation of hair, teeth, and sweat glands due to mutations in the ED1 gene located in the X chromosome coding for ectodysplasin 1. Ectodysplasin 1 is a novel trimeric transmembrane protein with an extracellular tumor necrosis factor (TNF)-like signalling domain that is believed to be involved in fetal development of ectodermal appendages such as the formation of hair follicles and tooth buds. Two isoforms of ectodysplasin 1, termed ED1-A1 and ED1-A2 arise by alternative splicing and bind to different receptors. Our pedigree of the four affected male calves, which were maternal halfsibs, indicates that the phenotype in cattle is also inherited as a monogenic X-linked recessive trait. We isolated a 480 kb BAC contig containing the complete bovine ED1 gene on BTA Xq22-q24. Physical mapping and sequence analysis of the coding parts of the ED1 gene revealed that a large genomic region including exon 3 of the ED1 gene is deleted in cattle with anhidrotic ectodermal dysplasia. RT-PCR confirmed that the ED1 mRNA from affected animals lacked the exon 3. Application of an RT-PCR assay showed the segregation of the causative large genomic deletion in the bovine ED1 gene. The demonstrated ED1 genotypes of eight family members confirmed the postulated X-linked recessive inheritance. As the clinical, pathological, and genetic findings in human ED1 show striking similarities to the described phenotype in cattle, this bovine disorder may serve as an animal model for human ED1. (Texte intégral)
| Main Authors: | , , |
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| Format: | conference_item biblioteca |
| Language: | eng |
| Published: |
CIRAD
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| Subjects: | L10 - Génétique et amélioration des animaux, résistance génétique, trouble génétique, bovin, http://aims.fao.org/aos/agrovoc/c_35130, http://aims.fao.org/aos/agrovoc/c_3217, http://aims.fao.org/aos/agrovoc/c_1391, |
| Online Access: | http://agritrop.cirad.fr/512066/ |
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