Aphakia (ak), a mouse mutation affecting early eye development: Fine mapping, consideration of candidate genes and altered Pax6 and Six3 gene expression pattern

The homozygous mouse mutant aphakia (ak) has been characterized by bilatera lly aphakic eyes without a pupil [Varnum DS, Stevens, LC (1968): J Hered 59 :147-150]. The mutation was mapped to chromosome 19 [Varnum DS, Stevens, LC (1975). Mouse News Lett 53:35]. Our linkage studies yielded a precise loca lization of the ok gene 0.6 +/- 0.3 cM proximal to the microsatellite marke r D19Mit10 and 0.7 +/- 0.4 cM distal to D19Mit4 and D19Mit91. No recombinat ion was found with the marker D19Mit9 among 418 backcross offspring tested. The developmental control gene Pax2 mapped 11.0 +/- 3.5 cM proximal to ok and is excluded as a candidate gene. Sequence analysis of Fgf8 and Chuk 1, which are localized close to the marker D19Mit10, detected no mutations in the ak/ak mutants. Histological analysis of homozygous mutants suggested th e arrest of lens development at the lens stalk stage, a transient morpholog ical structure during the formation of the lens vesicle. In the lens remnan ts, Pax6 and Six3 are expressed, whereas in the persisting lens stalk only Pax6 was detected. The expression pattern of Pax2 appeared normal, Cryaa ex pression could not be detected. As a consequence of the arrested lens devel opment, other ocular tissues that require for their development information from the intact lens, such as iris, ciliary muscle, retina, and vitreous b ody, are absent or Formed abnormally. Dev. Genet. 23:299-316, 1998. (C) 199 8 Wiley-Liss, Inc.