INRA, UMR1313, Unité de Génétique Animale et Biologie Intégrative, INRA, Jouy-en-Josas, France.
PLoS One. 2011 Apr 28;6(4):e19281. doi: 10.1371/journal.pone.0019281.
The fur of common rabbits is constituted of 3 types of hair differing in length and diameter while that of rex animals is essentially made up of amazingly soft down-hair. Rex short hair coat phenotypes in rabbits were shown to be controlled by three distinct loci. We focused on the "r1" mutation which segregates at a simple autosomal-recessive locus in our rabbit strains. A positional candidate gene approach was used to identify the rex gene and the corresponding mutation. The gene was primo-localized within a 40 cM region on rabbit chromosome 14 by genome scanning families of 187 rabbits in an experimental mating scheme. Then, fine mapping refined the region to 0.5 cM (Z = 78) by genotyping an additional 359 offspring for 94 microsatellites present or newly generated within the first defined interval. Comparative mapping pointed out a candidate gene in this 700 kb region, namely LIPH (Lipase Member H). In humans, several mutations in this major gene cause alopecia, hair loss phenotypes. The rabbit gene structure was established and a deletion of a single nucleotide was found in LIPH exon 9 of rex rabbits (1362delA). This mutation results in a frameshift and introduces a premature stop codon potentially shortening the protein by 19 amino acids. The association between this deletion and the rex phenotype was complete, as determined by its presence in our rabbit families and among a panel of 60 rex and its absence in all 60 non-rex rabbits. This strongly suggests that this deletion, in a homozygous state, is responsible for the rex phenotype in rabbits.
普通家兔的皮毛由 3 种不同长度和直径的毛发组成，而雷克斯动物的皮毛主要由惊人柔软的绒毛组成。雷克斯短毛兔的表型由三个不同的基因座控制。我们关注的是“r1”突变，它在我们的兔品系中分离在一个简单的常染色体隐性基因座上。使用定位候选基因方法来鉴定 rex 基因和相应的突变。该基因通过基因组扫描家族在实验交配方案中对 187 只兔子进行了定位，位于兔子 14 号染色体上的 40cM 区域内。然后，精细映射通过对另外 359 只后代进行基因分型，将该区域细化到 0.5cM（Z=78），这些后代携带或新生成了第一个定义间隔内的 94 个微卫星。比较作图指出，在这个 700kb 区域内有一个候选基因，即 LIPH（脂肪酶 H）。在人类中，这个主要基因的几个突变导致脱发、毛发缺失的表型。建立了兔基因结构，并在雷克斯兔的 LIPH 外显子 9 中发现了一个单核苷酸缺失（1362delA）。这种突变导致移码，并引入一个提前的终止密码子，可能使蛋白质缩短 19 个氨基酸。通过在我们的兔家族中存在该缺失，并在 60 只雷克斯兔及其 60 只非雷克斯兔中不存在，确定了该缺失与雷克斯表型之间的完全关联。这强烈表明，这种缺失在纯合状态下，是导致兔子雷克斯表型的原因。
