Ift43-KO Mouse

Ift43, also known as C14ORF179, is a subunit of the IFT-A complex involved in intraflagellar transport (IFT). IFT is crucial for the formation and maintenance of cilia, which play vital roles in signal transduction pathways like the hedgehog pathway, especially important in skeletal development [4,5].

Mutations in Ift43 have been linked to multiple disorders. In a Pakistani family, a novel homozygous mutation in Ift43 caused non-syndromic recessive retinal degeneration, with mutant Ift43 leading to shorter cilia in transfected cells [1]. In Chlamydomonas, an ift43 null or partial-deletion mutant had no or short flagella, and loss of Ift43 resulted in instability of IFT-A [2]. Mutations in Ift43 also led to a form of short rib polydactyly syndrome with distinctive campomelia, disrupting cilia formation and cartilage growth plate architecture [3]. In Sensenbrenner syndrome patients, mutations in Ift43 disturbed retrograde ciliary transport, causing accumulation of IFT-B proteins at the ciliary tip [4].

In conclusion, Ift43 is essential for ciliogenesis and normal ciliary function. Studies on Ift43, especially through loss-of-function models, have revealed its significance in various diseases such as retinal degeneration, short rib polydactyly syndrome, and Sensenbrenner syndrome. These findings help in understanding the underlying mechanisms of these ciliopathy-related disorders.

References:

1. Biswas, Pooja, Duncan, Jacque L, Ali, Muhammad, Riazuddin, S Amer, Ayyagari, Radha. . A mutation in IFT43 causes non-syndromic recessive retinal degeneration. In Human molecular genetics, 26, 4741-4751. doi:10.1093/hmg/ddx356. https://pubmed.ncbi.nlm.nih.gov/28973684/

2. Zhu, Bing, Zhu, Xin, Wang, Limei, Feng, Qianqian, Pan, Junmin. 2017. Functional exploration of the IFT-A complex in intraflagellar transport and ciliogenesis. In PLoS genetics, 13, e1006627. doi:10.1371/journal.pgen.1006627. https://pubmed.ncbi.nlm.nih.gov/28207750/

3. Duran, Ivan, Taylor, S Paige, Zhang, Wenjuan, Cohn, Daniel H, Krakow, Deborah. 2017. Mutations in IFT-A satellite core component genes IFT43 and IFT121 produce short rib polydactyly syndrome with distinctive campomelia. In Cilia, 6, 7. doi:10.1186/s13630-017-0051-y. https://pubmed.ncbi.nlm.nih.gov/28400947/

4. Arts, Heleen H, Bongers, Ernie M H F, Mans, Dorus A, Knoers, Nine V A M, Roepman, Ronald. 2011. C14ORF179 encoding IFT43 is mutated in Sensenbrenner syndrome. In Journal of medical genetics, 48, 390-5. doi:10.1136/jmg.2011.088864. https://pubmed.ncbi.nlm.nih.gov/21378380/

5. Huber, Celine, Cormier-Daire, Valerie. 2012. Ciliary disorder of the skeleton. In American journal of medical genetics. Part C, Seminars in medical genetics, 160C, 165-74. doi:10.1002/ajmg.c.31336. https://pubmed.ncbi.nlm.nih.gov/22791528/