Genetics Program, Michigan State University, East Lansing, MI 48824, USA.
J Hered. 2011 Sep-Oct;102 Suppl 1:S32-9. doi: 10.1093/jhered/esr031.
Feline spinal muscular atrophy (SMA) is an autosomal recessive juvenile onset lower motor neuron disease caused by an ∼ 140 kb deletion that disrupts expression of 2 genes, limb expression 1 (LIX1) and leucyl/cystinyl aminopeptidase (LNPEP). A previously generated Lnpep knockout (KO) mouse did not demonstrate a neuromuscular phenotype. Little is known about LIX1, except that it is evolutionarily conserved and highly expressed in spinal cord motor neurons. To determine whether loss of LIX1 alone is responsible for the feline SMA phenotype, a Lix1 intron 1 gene trap KO mouse line was obtained from Lexicon Genetics, Inc. Mating of F(1) heterozygotes produced offspring in the expected Mendelian ratios. KO and normal littermates were studied through 2 years of age by hanging latency, rotarod, inked footprint analysis, and histological methods. Disruption of Lix1 expression did not affect survival nor result in any neuromuscular phenotype. Reverse transcriptase-PCR amplification of spinal cord RNA identified a Lix1 alternative transcript beginning in intron 4 and containing exons 5 and 6. The alternative transcript appeared to be rodent specific, and its expression was not disrupted in Lix1 KO mice. Expression of the alternative transcript may have compensated for the loss of Lix1 in the KO mice and thus protected against motor neuron degeneration.
猫的脊髓性肌萎缩症（SMA）是一种常染色体隐性幼年起病的下运动神经元疾病，由大约 140kb 的缺失引起，该缺失破坏了 2 个基因的表达，即 LIM 结构域 1（LIX1）和亮氨酰/胱氨酰氨基肽酶（LNPEP）。之前生成的 LNPEP 敲除（KO）小鼠没有表现出神经肌肉表型。对 LIX1 的了解甚少，只知道它在进化上是保守的，并且在脊髓运动神经元中高度表达。为了确定单独缺失 LIX1 是否是猫 SMA 表型的原因，从 Lexicon Genetics，Inc.获得了 LIX1 内含子 1 基因捕获 KO 小鼠品系。F1 杂合子的交配产生了预期的孟德尔比例的后代。通过悬挂潜伏期、转棒、墨迹脚印分析和组织学方法对 KO 和正常同窝仔鼠进行了 2 年的研究。Lix1 表达的破坏不影响存活，也不会导致任何神经肌肉表型。脊髓 RNA 的逆转录 PCR 扩增鉴定出一种 Lix1 替代转录本，其起始于内含子 4 并包含外显子 5 和 6。替代转录本似乎是啮齿动物特异性的，并且在 Lix1 KO 小鼠中其表达没有受到破坏。替代转录本的表达可能补偿了 KO 小鼠中 Lix1 的缺失，从而防止了运动神经元退化。
