The spontaneous juvenile alopecia (jal) mutation in mice is associated with the insertion of an IAP element in the Gata3 gene

Abstract

Background: A combination of genetic fine-mapping and complementation testing was used previously to assign the juvenile alopecia mutation (abbreviated jal) to the GATA binding protein 3 (Gata3) gene on Chromosome 2 in mice. However, sequence analysis of Gata3 exons (including coding and noncoding regions) revealed no differences between wild type C3H/HeJ and co-isogenic C3H/HeJ-jal/J mutant mice. Results: Using a PCR-based scanning method, here we have tested the hypothesis that jal might result from insertion of a transposable element in or near the Gata3 gene. We show that the jal mutation is specifically associated with an intracisternal A particle (IAP) element of the I∆1 subtype that has transposed to Intron 3–4 in the Gata3 gene, and use the same panel of recombinants used previously to fine-map jal to show that this IAP element and jal are located within the same small genetic interval. Conclusion: Transposition of an IAP element of the I∆1 subtype into Intron 3–4 of the mutant Gata3^jal allele is the likely cause of the juvenile alopecia phenotype in mutant mice.

Keywords:

• retrotransposition
• germline mutation
• insertional mutagenesis
• focal alopecia
• mouse model

Public Interest Statement

In previous work, a recessive form of progressive hair loss known as juvenile alopecia was assigned to the Gata3 gene on mouse Chromosome 2, but no DNA defect was discovered. In this report, we identify a retrovirus-like element that is integrated within the Gata3^jal allele and is the likely cause of the mutant phenotype. This mutational mechanism would explain the variable expressivity of the hair loss phenotype in juvenile alopecia mice, and suggests that these animals may serve as a living resource for the further study of epigenetic gene regulation.

Competing interests

The authors declare no competing interests.

Acknowledgments

The authors thank Mary Mantzaris for excellent animal care.

Additional information

Funding

This study was supported by a small research grant from the Connecticut State University System [grant number ARKINJ].

Notes on contributors

Thomas R. King

The research group led by Thomas R. King at Central Connecticut State University (New Britain, CT) aims to identify the genetic basis of spontaneous hair variants in mice and rats. Identification of such causative gene mutations can make probes available for the molecular analysis of both normal and disrupted development of the mammalian integument, and can help to identify human conditions these animal resources might model. Malcolm E. Connor is a graduate student in the Department of Biomolecular Sciences.