CRISPR/Cas9-mediated deletion of Fam83h induces defective tooth mineralization and hair development in rabbits.
CRISPR/Cas9-mediated deletion of Fam83h induces defective tooth mineralization and hair development in rabbits.
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DOI：
10.1111/jcmm.17597
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发表时间：
2022-11
影响因子：
5.3
通讯作者：
中科院分区：
文献类型：
--
作者：
具有83个序列相似性的家族成员H(Fam83h)是牙釉质形成所必需的。Fam83h突变导致人类成釉不全(AI)，这是一种以牙釉质严重硬度缺陷为特征的遗传性疾病。然而，先前的研究表明，Fam83h基因敲除/LacZ敲除小鼠中没有釉质缺陷。在本研究中，通过双重sgRNA导向的CRISPR/CAS9系统在兔体内产生了大量的Fam83h基因缺失(900scispr/ 。纯合子FAM83h基因敲除兔(FAM83h−/−)与WT兔相比，牙齿矿化异常，牙本质疏松。此外，FAM83h−/−兔背部皮肤毛囊数量减少，毛发循环障碍和毛干分化缺陷。此外，X线和骨切片染色显示，FAM83h−/−兔尺骨和桡骨异常弯曲，尺骨关节表面松质骨量不足。综上所述，这些数据是FAM83h−/−兔毛发周期缺陷、毛干分化以及尺骨和桡骨异常弯曲的首次报道。这种新型的Fam83h−/−兔模型有助于了解Fam83h的功能及其突变的致病机制。
Family with sequence similarity 83 members H (Fam83h) is essential for dental enamel formation. Fam83h mutations cause human amelogenesis imperfecta (AI), an inherited disorder characterized by severe hardness defects in dental enamel. Nevertheless, previous studies showed no enamel defects in Fam83h‐knockout/lacZ‐knockin mice. In this study, a large deletion of the Fam83h gene (900 bp) was generated via a dual sgRNA‐directed CRISPR/Cas9 system in rabbits. Abnormal tooth mineralization and loose dentine were found in homozygous Fam83h knockout (Fam83h −/−) rabbits compared with WT rabbits. In addition, reduced hair follicle counts in dorsal skin, hair cycling dysfunction and hair shaft differentiation deficiency were observed in Fam83h −/− rabbits. Moreover, X‐rays and staining of bone sections showed abnormal bending of the ulna and radius and an ulnar articular surface with insufficient trabecular bone in Fam83h −/− rabbits. Taken together, these data are the first report of defective hair cycling, hair shaft differentiation and abnormal bending of the ulna and radius in Fam83h −/− rabbits. This novel Fam83h −/− rabbit model may facilitate understanding the function of Fam83h and the pathogenic mechanism of the Fam83h mutation.
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影响因子：
7.6
作者：
Wright JT;Frazier-Bowers S;Simmons D;Alexander K;Crawford P;Han ST;Hart PS;Hart TC
通讯作者：
Hart TC
影响因子：
4
作者：
Smith CEL;Kirkham J;Day PF;Soldani F;McDerra EJ;Poulter JA;Inglehearn CF;Mighell AJ;Brookes SJ
通讯作者：
Brookes SJ
影响因子：
2.7
作者：
Pujades, C;Kamaid, A;Giraldez, F
通讯作者：
Giraldez, F
影响因子：
3.9
作者：
Bozatzi P;Sapkota GP
通讯作者：
Sapkota GP
影响因子：
3.9
作者：
Lee, Sook-Kyung;Hu, Jan C-C;Bartlett, John D;Lee, Kyung-Eun;Lin, Brent P-J;Simmer, James P;Kim, Jung-Wook
通讯作者：
Kim, Jung-Wook