Smad4-Flox

品系全名

C57BL/6Smoc-Smad4tm1(flox)Smoc

目录号

NM-CKO-18011

品系状态

活体

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基因信息

基因名
Smad4

基因曾用名

DPC4; Madh4; AW743858; D18Wsu70e

NCBI ID

17128

MGI ID

894293

Ensembl ID

ENSMUSG00000024515

Pubmed

Smad4

人类同源基因

SMAD4

品系描述

Smad4最初是在胰腺癌中发现的，也被称为Deleted in Pancreatic Carcinoma Locus 4 (DPC4), 其缺失和突变率为50%， 并是胰腺癌诊断中的一个重要标志物。Smad4在众多肿瘤中缺失或突变，尤其是在消化系肿瘤， 发挥抑癌基因功能，与肿瘤的侵袭、远处转移、国际抗癌联盟肿瘤TNM分期有密切关系。Smad4通过转化生长因子β（TGFβ）和骨形态发生蛋白（BMP）信号通路将信号从细胞表面传递到细胞核，参与发育过程中的生长控制和转录调控。 将loxp位点插入到exon3-4区域两侧，构建Smad4基因条件性敲除小鼠模型。可与组织特异性Cre工具鼠交配，获得在特定细胞类型中敲除Smad4基因的小鼠模型，可用于研究细胞增殖和肿瘤抑制。例如：与在胰腺特异表达Cre工具鼠交配后可用于研究胰腺导管异常和胰腺癌。 Smad4基因全身敲除纯合子小鼠在原肠胚形成之前表现出胚外膜和内胚层受损并引发死亡。全身敲除杂合子小鼠会发生腺胃和十二指肠的息肉。

疾病预测

成骨不全症
Osteogenesis Imperfecta

近似模型的表型

MGI:5604139
注：该品系与Sp7-tTA,tetO-EGFP/cre工具鼠交配才可能获得预期表型

参考文献

Salazar VS, Zarkadis N, Huang L, Norris J, Grimston SK, Mbalaviele G, Civitelli R, Embryonic ablation of osteoblast Smad4 interrupts matrix synthesis in response to canonical Wnt signaling and causes an osteogenesis-imperfecta-like phenotype. J Cell Sci. 2013 Nov 1;126(Pt 21):4974-84

鳞状细胞癌
Squamous Cell Carcinoma

近似模型的表型

MGI:5556259
注：该品系与Kras-LSL-G12D(NM-KI-190003)和Krt1-15-cre工具鼠交配才可能获得预期表型

参考文献

White RA, Neiman JM, Reddi A, Han G, Birlea S, Mitra D, Dionne L, Fernandez P, Murao K, Bian L, Keysar SB, Goldstein NB, Song N, Bornstein S, Han Z, Lu X, Wisell J, Li F, Song J, Lu SL, Jimeno A, Roop DR, Wang XJ, Epithelial stem cell mutations that promote squamous cell carcinoma metastasis. J Clin Invest. 2013 Oct 1;123(10):4390-404

胃癌
Stomach Cancer

近似模型的表型

MGI:5634400
注：该品系与Cdh1-Flox(NM-CKO-18016)，P53-Flox(2)(NM-CKO-190067)和Pdx1-cre工具鼠交配才可能获得预期表型

参考文献

Park JW, Jang SH, Park DM, Lim NJ, Deng C, Kim DY, Green JE, Kim HK, Cooperativity of E-cadherin and Smad4 Loss to Promote Diffuse-Type Gastric Adenocarcinoma and Metastasis. Mol Cancer Res. 2014 Aug;12(8):1088-99

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