Generation of Ttpa−/− mice.
(A) Strategy for disrupting the Ttpa
gene. On homologous recombination of the targeting vector with the
Ttpa locus, lacZ (β-galactosidase) and
neo genes are inserted into the 5′ untranslated
sequences of exon 1, resulting in the deletion of the
Ttpa translational start codon. A,
B, and C represent primers used for PCR
genotyping. (B) Southern blot analysis of genomic DNA
from offspring of heterozygous intercrosses. (C) Absence
of α-TTP protein in liver homogenates of
Ttpa−/− mice. α-TTP protein levels
were reduced by ≈50% in Ttpa+/− mice.
(D) α-Tocopherol levels in
Ttpa+/+Apoe+/+
and
Ttpa−/−Apoe+/+
mice and in
Ttpa+/+Apoe−/−
and
Ttpa−/−Apoe−/−
mice, of 7–12 months of age. Aortic γ-tocopherol levels were
similarly low in both
Ttpa+/+Apoe−/−
and
Ttpa−/−Apoe−/−
mice (0.60 ± 0.64 vs. 0.77 ± 0.68 nmol/g,
P = 0.55). Data are expressed as mean ± SD.