Abstract:
:The agouti gene regulates the differential production of eumelanin (black or brown) and phaeomelanin (yellow) pigment granules by melanocytes in the hair follicles of mice. The original nonagouti (a) allele, which confers a predominantly black coat color, has been shown to revert to two other more dominant agouti alleles, black-and-tan (a(t)) and white-bellied agouti (Aw), with an exceptionally high frequency. The a(t) and Aw alleles confer phenotypes in which the pigmentation is not uniformly distributed over the dorsal and ventral surfaces of the animal; in both cases the ventral surface of the animal is markedly lighter than the dorsal surface due to an increase in phaeomelanin production. To understand the unusually high reversion rate of a to a(t) or Aw, and to decipher the molecular events associated with the different pigmentation patterns associated with these three agouti alleles, we have characterized a, a(t) and Aw at the molecular level. Here, we report that insertions of 11, 6, and 0.6 kb are present at precisely the same position in the first intron of the agouti gene in a, a(t), and Aw, respectively. The a insertion consists of a 5.5-kb VL30 element that has incorporated 5.5 kb of additional sequence internally; this internal sequence is flanked by 526-bp direct repeats. The a(t) allele contains only the VL30 element and a single, internal 526-bp repeat. The Aw allele has only a solo VL30 LTR. Based on the comparison of the structure of the a(t) and Aw insertions, we propose that reverse mutations occur by excision of inserted sequences in a through homologous recombination, utilizing either the 526-bp direct repeats to generate a(t) or the VL30 LTRs to generate Aw. Moreover, the analysis of these three alleles has allowed us to identify additional exons of the agouti gene that give rise to alternatively processed forms of agouti mRNA. We demonstrate that the distinct insertions in a, a(t) and Aw cause pigmentation differences by selectively inactivating the expression of different forms of agouti transcripts.
journal_name
Genes Devjournal_title
Genes & developmentauthors
Bultman SJ,Klebig ML,Michaud EJ,Sweet HO,Davisson MT,Woychik RPdoi
10.1101/gad.8.4.481subject
Has Abstractpub_date
1994-02-15 00:00:00pages
481-90issue
4eissn
0890-9369issn
1549-5477journal_volume
8pub_type
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