The microphthalmia-associated transcription factor (Mitf) gene and its role in regulating eye function

• Published in: Scientific reports Vol. 9; no. 1; pp. 15386 - 12
• Main Authors: García-Llorca, Andrea, Aspelund, Snaefridur Gudmundsdottir, Ogmundsdottir, Margret Helga, Steingrimsson, Eiríkur, Eysteinsson, Thor
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 28-10-2019; Nature Publishing Group
• Subjects: 14/34; 59/5; 631/378/3917; 64/60; 692/4017; 9/10; 9/30; Angiography; Animals; Degeneration; Electroretinograms; Epithelium; Eye; Eye Color; Heterozygote; Homozygote; Humanities and Social Sciences; Mice; Mice, Inbred C57BL; Microphthalmia-associated transcription factor; Microphthalmia-Associated Transcription Factor - genetics; Microphthalmia-Associated Transcription Factor - metabolism; Microphthalmos - genetics; Microphthalmos - pathology; multidisciplinary; Mutation; Pigmentation; Retina; Retinal pigment epithelium; Retinal Pigment Epithelium - metabolism; Retinal Pigment Epithelium - pathology; Retinal Vessels - pathology; Retinal Vessels - physiopathology; Science; Science (multidisciplinary); Structure-function relationships; Transcription factors
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-019-51819-0

Mutations in the microphthalmia-associated transcription factor (
Mitf
) gene can cause retinal pigment epithelium (RPE) and retinal dysfunction and degeneration. We examined retinal and RPE structure and function in 3 month old mice homo- or heterozygous or compound heterozygous for different
Mitf
mutations (
Mitf
mi
-
vga9
/+
,
Mitf
mi
-
enu22
(
398
)
/
Mitf
mi
-
enu22
(
398
)
,
Mitf
Mi
-
Wh
/+
and
Mitf
Mi
-
Wh
/
Mitf
mi
) which all have normal eye size with apparently normal eye pigmentation. Here we show that their vision and retinal structures are differentially affected. Hypopigmentation was evident in all the mutants while bright-field fundus images showed yellow spots with non-pigmented areas in the
Mitf
mi
-
vga9
/+
mice.
Mitf
Mi
-
Wh
/+
and
Mitf
Mi
-
Wh
/
Mitf
mi
mice showed large non-pigmented areas. Fluorescent angiography (FA) of all mutants except
Mitf
mi
-
vga9
/+
mice showed hyperfluorescent areas, whereas FA from both
Mitf
-
Mi
-
Wh
/+
and
Mitf
Mi
-
Wh
/
Mitf
mi
mice showed reduced capillary network as well as hyperfluorescent areas. Electroretinogram (ERG) recordings show that
Mitf
Mi
-
Wh
/+
and
Mitf
Mi
-
Wh
/
Mitf
mi
mice are severely impaired functionally whereas the scotopic and photopic ERG responses of
Mitf
mi
-
vga9
/+
and
Mitf
mi
-
enu22
(
398
)
/
Mitf
mi
-
enu22
(
398
)
mice were not significantly different from wild type mice. Histological sections demonstrated that the outer retinal layers were absent from the
Mitf
Mi
-
Wh
/+
and
Mitf
Mi
-
Wh
/
Mitf
mi
blind mutants. Our results show that
Mitf
mutations affect eye function, even in the heterozygous condition and that the alleles studied can be arranged in an allelic series in this respect.