The Elovl4 gene encodes a is required for the synthesis of very long chain saturated fatty acids and very long chain polyunsaturated fatty acids (chain length longer
than C > 26). Mutations and small deletions in the human ELOVl4 gene are associated with Stargardt-like macular dystrophy (STGD3) and autosomal dominant Stargardt-like macular dystrophy (ADMD), also referred to as autosomal dominant atrophic macular degeneration. These mice carry a targeted mutation of the Elovl4 gene in which a 5bp deletion was introduced in exon 6, which is equivalent to a known human mutation.
Mutant gene products (mRNA and protein) are detected by qRT-PCR and Western blot analysis of skin from homozygous pups.
Mice that are heterozygous for the targeted mutation are viable and fertile. Homozygotes die a few hours after birth. At birth homozygous mice exhibit scaly, wrinkled skin, with severely compromised epidermal permeability barrier function.
Heterozygotes have lower levels of long chain fatty acids in retinal tissue compared to wildtype controls. As early as 2 months of age, ultrastructural abnormalities are observed in cone photoreceptors. As the mice age, there is progressive accumulation of lipofuscin in retinal pigment epithelium (RPE) and subretinal deposits, debris in the subretinal space and vacuoles in the RPE.
By 6 months, heterozygotes exhibit a significant loss of cone photoreceptors. In mutant mice 8 months in age, electroretinograms (ERGs) are abnormal, with elevated b- and a-wave amplitudes.
At approximately 10 months of age, rod outer segments appear shortened.
