A new mouse model for retinal degeneration due to Fam161a deficiency

Sci Rep. 2021 Jan 21;11(1):2030. doi: 10.1038/s41598-021-81414-1.


FAM161A mutations are the most common cause of inherited retinal degenerations in Israel. We generated a knockout (KO) mouse model, Fam161atm1b/tm1b, lacking the major exon #3 which was replaced by a construct that include LacZ under the expression of the Fam161a promoter. LacZ staining was evident in ganglion cells, inner and outer nuclear layers and inner and outer-segments of photoreceptors in KO mice. No immunofluorescence staining of Fam161a was evident in the KO retina. Visual acuity and electroretinographic (ERG) responses showed a gradual decrease between the ages of 1 and 8 months. Optical coherence tomography (OCT) showed thinning of the whole retina. Hypoautofluorescence and hyperautofluorescence pigments was observed in retinas of older mice. Histological analysis revealed a progressive degeneration of photoreceptors along time and high-resolution transmission electron microscopy (TEM) analysis showed that photoreceptor outer segment disks were disorganized in a perpendicular orientation and outer segment base was wider and shorter than in WT mice. Molecular degenerative markers, such as microglia and CALPAIN-2, appear already in a 1-month old KO retina. These results indicate that a homozygous Fam161a frameshift mutation affects retinal function and causes retinal degeneration. This model will be used for gene therapy treatment in the future.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calpain / genetics*
  • Disease Models, Animal
  • Electroretinography
  • Eye Proteins / genetics*
  • Frameshift Mutation / genetics
  • Humans
  • Lac Operon / genetics
  • Mice
  • Mice, Knockout
  • Retina / diagnostic imaging*
  • Retina / pathology
  • Retinal Degeneration / diagnostic imaging
  • Retinal Degeneration / genetics*
  • Retinal Degeneration / pathology
  • Retinitis Pigmentosa / genetics
  • Retinitis Pigmentosa / pathology
  • Tomography, Optical Coherence
  • Visual Acuity / genetics


  • Eye Proteins
  • Fam161A protein, mouse
  • Calpain
  • Capn2 protein, mouse