Involvement of Clustered Genes in Mammalian Functions: Their Relation in a Rat Mutant Strain.
Involvement of Clustered Genes in Mammalian Functions: Their Relation in a Rat Mutant Strain.
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哺乳动物功能中簇状基因的参与：它们在大鼠突变株中的关系。
DOI：
10.1007/s00239-017-9788-6
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发表时间：
2017
影响因子：
3.9
通讯作者：
Shigeki Tsuchida.
中科院分区：
文献类型：
--
作者：
Naoki Nanashima;Toshiyuki Yamada;Takeshi Shimizu;Shigeki Tsuchida.
2009)。hrs的无毛表型是由于80 kb基因组DNA的缺失，从Kb25的外显子9 （Krt85）到Krt2-25的外显子9（图2a）。Krt85和Krt2-25的断点位于两个基因共享的95bp范围内，表明缺失是由非等位基因同源重组引起的（Nanashima et al. 2008）。以硬角蛋白为基础的毛发、泌乳和乳腺都是哺乳动物的共同特征（McClellan et al. 2008）。女性hhr在哺乳期早期表现出乳腺的退化（Nanashima et al. 2005）。阵列比较基因组杂交显示hrs中1q21缺失了50 kb的基因组DNA，包括Pla2g4c基因和邻近的LOC691813基因（图2b， Nanashima et al. 2015）。这两个基因是高度同源的，它们的断点在一个共享的149-bp区域内。抑制Pla2g4c在大鼠乳腺细胞中的表达，表明其参与防止细胞凋亡的诱导。在HHR胸腺中，自然产生的Treg （nTreg）数量减少。染色体4q42区的Ly49基因：Ly49s3、s4、i3和i4在hhr中缺失（图2c）。在这些基因中，Ly49s3基因在野生型sdr胸腺树突状细胞中表达，而在hhr中不表达。通过与SDR树突状细胞共培养，cd4阳性的SDR胸腺细胞可以分化为nTreg，而HHR树突状细胞缺乏诱导nTreg分化的能力（Yamada et al. 2013）。通过在HHR树突状细胞中强制表达Ly49s3，证明了Ly49s3直接参与诱导nTreg分化。
2009). The hairless phenotype of HHRs is due to the deletion of an 80-kb genomic DNA, ranging from exon 9 of Kb25 (Krt85) to exon 9 of Krt2-25 (Fig. 2 a). The breakpoints of Krt85 and Krt2-25 are within a 95-bp portion shared by the two genes, indicating that the deletion is due to non-allelic homologous recombination (Nanashima et al. 2008). Hard keratin-based hair, lactation, and mammary glands are all characteristics common in mammals (McClellan et al. 2008). Female HHRs show involution of the mammary glands at an early stage of lactation (Nanashima et al. 2005). Array comparative genomic hybridization revealed the deletion of 50 kb of genomic DNA from 1q21 in HHRs, including the Pla2g4c gene and neighboring LOC691813 gene (Fig. 2 b, Nanashima et al. 2015). Both genes are highly homologous and their breakpoints are within a shared 149-bp region. Inhibition of Pla2g4c expression in rat mammary cells has revealed that it is involved in the prevention of apoptosis induction. In the HHR thymus, the number of naturally occurring Treg (nTreg) was decreased. The Ly49 genes: Ly49s3, s4, i3, and i4, in the chromosome 4q42 region, are deleted in HHRs (Fig. 2 c). Among these genes, the Ly49s3 gene is expressed in thymic dendritic cells in wild-type SDRs, but not in HHRs. CD4-positive SDR thymocytes can be differentiated to nTreg by co-culture with SDR dendritic cells, whereas HHR dendritic cells show deficient induction of nTreg differentiation (Yamada et al. 2013). The direct involvement of Ly49s3 in the induction of nTreg differentiation is demonstrated by forced expression of Ly49s3 in HHR dendritic cells.