Mammalian Genome

, Volume 18, Issue 4, pp 270–276 | Cite as

Ocular defects associated with a null mutation in the mouse arylamine N-acetyltransferase 2 gene

  • Larissa Wakefield
  • Hilary Long
  • Nathan Lack
  • Edith Sim


The xenobiotic metabolizing enzyme, mouse arylamine N-acetyltransferase type 2 (Nat2), is expressed during embryogenesis from the blastocyst stage and in the developing neural tube and eye. Mouse Nat2 is widely believed to have an endogenous role distinct from xenobiotic metabolism, and polymorphisms in the human ortholog have been implicated in susceptibility to spina bifida and orofacial clefting. The developmental role of Nat2 was investigated using transgenic Nat2 knockout/lacZ knockin (Nat2 tm1Esim) mice. The transgene was bred onto an A/J background and offspring were scored for developmental defects at weaning. After backcross generation eight, an ocular defect, ranging from cataract to microphthalmia and anophthalmia, was recorded among offspring of backcross and intercross pairs. Histologic analysis of cataract cases revealed a failure of the lens to separate from the cornea and plaques within the lens tissue. While Nat2 −/− mice have been described as overtly aphenotypic, the presence of a Nat2 null allele in one or both parents can result in ocular defects. These ocular phenotypes and their association with Nat2 genotype indicate that the Nat2 locus may be responsible for the previously described microphthalmic Cat4 phenotype and implicate the orthologous human NAT as a phenotypic modifier of microphthalmia and anophthalmia.


Cataract Spina Bifida Slow Acetylator Microphthalmia Nat2 Genotype 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



The authors thank Peter Mackenzie and Colin Ackerman for useful discussion and critical reading of the manuscript and Tim Heaton for advice on statistical analysis. This work was funded by the Wellcome Trust and by an NSERT postgraduate scholarship and a Canadian national scholarship to NL.


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Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Larissa Wakefield
    • 1
  • Hilary Long
    • 1
  • Nathan Lack
    • 1
  • Edith Sim
    • 1
  1. 1.Department of PharmacologyUniversity of OxfordOxfordUK

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