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Confirmation of the role of N‐acetyltransferase 2 in teratogen‐induced cleft palate using transgenics and knockouts
Author(s) -
Erickson Robert P.,
Cao Wen,
Acuña Diana K.,
Strnatka Diana W.,
Hunter Robert J.,
Chau Binh T.,
Wakefield Larissa V.,
Sim Edith,
McQueen Charlene A.
Publication year - 2008
Publication title -
molecular reproduction and development
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.745
H-Index - 105
eISSN - 1098-2795
pISSN - 1040-452X
DOI - 10.1002/mrd.20852
Subject(s) - biology , teratology , inbred strain , genetics , gene knockout , knockout mouse , strain (injury) , heterozygote advantage , ratón , endocrinology , gene , genotype , anatomy , fetus , pregnancy
Abstract Previous work on Dilantin‐ and hydrocortisone‐induced cleft palate and cleft lip with or without cleft palate using congenics for the N‐acetyltransferase loci ( Nat1 and Nat2 are closely linked) and recombinant inbred lines implicated the Nat1,2 region in susceptibility to teratogen‐induced orofacial clefting. Since Nat1 does not differ between the two strains, Nat2 appeared to be responsible. We have now tested this conclusion using transgenics and knockouts. Transgenics for human NAT1 (equivalent to mouse Nat2 ) and knockouts for Nat2 were tested for susceptibility to Dilantin, hydrocortisone, and 6‐aminonicotinamide‐induced orofacial clefting. We found that Nat2 greatly influences teratogen‐induced orofacial clefting on the A/J background but not on the C57BL/6J background. The magnitude and direction of the effects depended on which teratogen was used. The Nat2 knockout did not make C57BL/6J susceptible or A/J (already with very low activity) more susceptible but significantly decreased sporadic clefting in the A/J strain. We conclude that only the A/J strain, with several loci affecting orofacial clefting, is influenced by Nat2 . Mol. Reprod. Dev. 75: 1071–1076, 2007. © 2007 Wiley‐Liss, Inc.