Mutanlallemand (mtl) and Belly Spot and Deafness (bsd) are two new mutations of Lmx1a causing severe cochlear and vestibular defects.
Mutanlallemand (mtl) and Belly Spot and Deafness (bsd) are two new mutations of Lmx1a causing severe cochlear and vestibular defects.
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DOI：
10.1371/journal.pone.0051065
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Steel KP
中科院分区：
文献类型：
--
作者：
Steffes G;Lorente-Cánovas B;Pearson S;Brooker RH;Spiden S;Kiernan AE;Guénet JL;Steel KP
mutanlallmand （mtl）和Belly Spot and Deafness （bsd）是小鼠Lmx1a基因中两个新的自发等位基因。纯合子突变体表现出头部晃动和盘旋的行为，表明前庭缺陷，它们有短尾巴和大小不一的白色腹部斑块。听觉脑干反应（ABR）分析表明，mtl和bsd纯合子是聋子，而杂合子和野生型的幼崽听力正常。E16.5的内耳染色显示mtl和bsd纯合子缺乏内淋巴管和半规管，耳蜗管短。这些新的等位基因与先前的（Lmx1a）突变体有相似之处。mtl与dreher、mtl与bsd的互补实验表明，mtl和bsd是Lmx1a基因的新突变等位基因。为了确定mtl和bsd突变小鼠的Lmx1a突变，我们进行了PCR，然后进行了基因组DNA和cDNA测序。mtl突变是外显子4 3 '剪接位点的单点突变，导致外显子延伸并激活下游44个碱基对的隐剪接位点，而bsd突变是包括外显子3的基因组缺失。这两种突变都会导致LMX1A蛋白截断，影响同源结构域（mtl）或lim2结构域（bsd），这对LMX1A蛋白的功能至关重要。此外，mtl和bsd突变体中Lmx1a转录物水平显著下调。在mtl和bsd突变体中，Hmx2/3和Pax2的表达也下调，表明这些转录因子的上游Lmx1a在早期内耳形态发生中起作用。我们发现，这些突变体虽然畸形，但也有感觉斑块。这两个新的Lmx1a等位基因的特征突出了该基因在耳蜗和前庭系统发育中的关键作用。
Mutanlallemand (mtl) and Belly Spot and Deafness (bsd) are two new spontaneous alleles of the Lmx1a gene in mice. Homozygous mutants show head tossing and circling behaviour, indicative of vestibular defects, and they have short tails and white belly patches of variable size. The analysis of auditory brainstem responses (ABR) showed that mtl and bsd homozygotes are deaf, whereas heterozygous and wildtype littermates have normal hearing. Paint-filled inner ears at E16.5 revealed that mtl and bsd homozygotes lack endolymphatic ducts and semicircular canals and have short cochlear ducts. These new alleles show similarities with dreher (Lmx1a) mutants. Complementation tests between mtl and dreher and between mtl and bsd suggest that mtl and bsd are new mutant alleles of the Lmx1a gene. To determine the Lmx1a mutation in mtl and bsd mutant mice we performed PCR followed by sequencing of genomic DNA and cDNA. The mtl mutation is a single point mutation in the 3′ splice site of exon 4 leading to an exon extension and the activation of a cryptic splice site 44 base pairs downstream, whereas the bsd mutation is a genomic deletion that includes exon 3. Both mutations lead to a truncated LMX1A protein affecting the homeodomain (mtl) or LIM2-domain (bsd), which is critical for LMX1A protein function. Moreover, the levels of Lmx1a transcript in mtl and bsd mutants are significantly down-regulated. Hmx2/3 and Pax2 expression are also down-regulated in mtl and bsd mutants, suggesting a role of Lmx1a upstream of these transcription factors in early inner ear morphogenesis. We have found that these mutants develop sensory patches although they are misshapen. The characterization of these two new Lmx1a alleles highlights the critical role of this gene in the development of the cochlea and vestibular system.
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影响因子：
3.7
作者：
Kim HM;Wangemann P
通讯作者：
Wangemann P
影响因子：
12.3
作者：
Hilton JM;Lewis MA;Grati M;Ingham N;Pearson S;Laskowski RA;Adams DJ;Steel KP
通讯作者：
Steel KP
BMP4对于检测角头运动的前庭设备的形成至关重要。
影响因子：
4.5
作者：
Chang, Weise;Lin, Zhengshi;Kulessa, Holger;Hebert, Jean;Hogan, Brigid L. M.;Wu, Doris K.
通讯作者：
Wu, Doris K.
影响因子：
2.5
作者：
Chizhikov, Victor;Steshina, Ekaterina;Millen, Kathleen J.
通讯作者：
Millen, Kathleen J.
DOI：
10.1007/bf00309744
发表时间：
1951-01-01
期刊：
ZEITSCHRIFT FUR INDUKTIVE ABSTAMMUNGS UND VERERBUNGSLEHRE
影响因子：
--
作者：
FALCONER, DS;SIERTSROTH, U
通讯作者：
SIERTSROTH, U