Faculty Collaboration Database

A spontaneous mutation in Srebf2 leads to cataracts and persistent skin wounds in the lens opacity 13 (lop13) mouse. Mamm Genome 2011 Dec;22(11-12):661-73

Date

08/23/2011

Pubmed ID

21858719

Pubmed Central ID

PMC3251904

DOI

10.1007/s00335-011-9354-2

Scopus ID

2-s2.0-84655163481 (requires institutional sign-in at Scopus site)   11 Citations

Abstract

Lens opacity 13 (lop13) is a spontaneous, autosomal recessive mouse mutant that exhibits nuclear cataracts. Histological analysis revealed swollen lens fiber cells and the presence of bladder cells within the lens cortex, as well as morgagnian globules and liquefied material at the lens posterior. At 3 months of age, in addition to cataracts, lop13 mice also develop persistent skin wounds. Linkage analysis assigned the lop13 locus to a 1.1-Mb region on mouse Chr 15, encompassing 19 candidate genes. Sequence analysis identified a C3112T mutation in exon 18 of Sterol Regulatory Element Binding-Transcription Factor 2 (Srebf2) resulting in the R1038C substitution of a highly conserved arginine within the Srebf2 regulatory domain. Srebf2 belongs to a family of membrane-bound basic helix-loop-helix leucine zipper transcription factors that control the expression of genes involved in the biosynthesis and uptake of cholesterol and fatty acids. The lack of complementation observed in Srebf2 ( lop13/GT ) compound heterozygotes carrying the Srebf2 gene trapped allele (Srebf2 ( GT )) provides genetic evidence that the identified C3112T substitution in Srebf2 is responsible for the lop13 phenotype. Gas chromatography analysis identified lower levels of cholesterol in the lop13 brain, liver, and lens when compared to wild-type mice. These findings suggest that lop13 is a hypomorphic mutation in Srebf2. As such, the lop13 mouse presents an invaluable in vivo model for studying the contribution of Srebf2 and cholesterol to maintaining the homeostasis of the lens and skin.

Author List

Merath KM, Chang B, Dubielzig R, Jeannotte R, Sidjanin DJ

Author

Danielle Sidjanin Maier PhD Nurse Practitioner in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Base Sequence
Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
Cataract
Cholesterol
Female
Genotype
Lens, Crystalline
Male
Mice
Mice, Inbred C57BL
Mutation
Sequence Analysis, DNA
Skin
Sterol Regulatory Element Binding Protein 2