Deletion in the Bardet-Biedl syndrome gene TTC8 results in a syndromic retinal degeneration in dogs

Sammanfattning

In golden retriever dogs, a 1 bp deletion in the canine TTC8 gene has been shown to cause progressive retinal atrophy (PRA), the canine equivalent of retinitis pigmentosa. In humans, TTC8 is also implicated in Bardet–Biedl syndrome (BBS). To investigate if the affected dogs only exhibit a non-syndromic PRA or develop a syndromic ciliopathy similar to human BBS, we recruited 10 affected dogs to the study. The progression of PRA for two of the dogs was followed for 2 years, and a rigorous clinical characterization allowed a careful comparison with primary and secondary characteristics of human BBS. In addition to PRA, the dogs showed a spectrum of clinical and morphological signs similar to primary and secondary characteristics of human BBS patients, such as obesity, renal anomalies, sperm defects, and anosmia. We used Oxford Nanopore long-read cDNA sequencing to characterize retinal full-length TTC8 transcripts in affected and non-affected dogs, the results of which suggest that three isoforms are transcribed in the retina, and the 1 bp deletion is a loss-of-function mutation, resulting in a canine form of Bardet–Biedl syndrome with heterogeneous clinical signs.

Nyckelord

Bardet–Biedl syndrome (BBS); primary cilia; ciliopathy; BBS8; progressive retinal atrophy (PRA); retinitis pigmentosa

Publicerad i

Genes
2020, volym: 11, nummer: 9, artikelnummer: 1090

SLU författare

• Mäkeläinen, Suvi

  • Institutionen för husdjurens biovetenskaper, Sveriges lantbruksuniversitet
    

• Van Der Heiden, Anna Darlene

  • Institutionen för husdjurens biovetenskaper, Sveriges lantbruksuniversitet
    

• Andersson, Elina

  • Institutionen för husdjurens biovetenskaper, Sveriges lantbruksuniversitet
    

• Thorsson, Elina

  • Institutionen för husdjurens biovetenskaper, Sveriges lantbruksuniversitet
    

• Ström Holst, Bodil

  • Institutionen för kliniska vetenskaper, Sveriges lantbruksuniversitet
    

• Häggström, Jens

  • Institutionen för kliniska vetenskaper, Sveriges lantbruksuniversitet
    

• Ljungvall, Ingrid

  • Institutionen för kliniska vetenskaper, Sveriges lantbruksuniversitet
    

• Andersson, Göran

  • Institutionen för husdjurens biovetenskaper, Sveriges lantbruksuniversitet
    

• Ekesten, Björn

  • Institutionen för kliniska vetenskaper, Sveriges lantbruksuniversitet
    

• Bergström, Tomas

  • Institutionen för husdjurens biovetenskaper, Sveriges lantbruksuniversitet
    

UKÄ forskningsämne

Klinisk vetenskap

Publikationens identifierare

• DOI: https://doi.org/10.3390/genes11091090

Permanent länk till denna sida (URI)

https://res.slu.se/id/publ/107781