Genetic background in apolipoprotein A-I and cystathionine beta-synthase deficiency.
Double heterozygous mice lacking one allele of Cbs and Apoa1 develop hyperhomocysteinemia and hypoalphalipoproteinemia together with moderate hypertension. To study the influence of the genetic background into this specific phenotype, four groups of male mice were established: control and double heterozygous groups in C57BL/6J and in C57BL/6J x 129 backgrounds, respectively. Nitric oxide levels, systolic blood pressure, plasma lipid parameters, arylesterase activity and aorta histology were analyzed as well as oligonucleotide array hybridization of liver RNA. Results demonstrated that double heterozygous mice in C57BL/6J substrate had a milder phenotype showing lower increase in blood pressure compared to double heterozygous group in hybrid background. The severity of the phenotype in the latter group was associated with lower nitric oxide and arylesterase activity levels, and hyperplasia of the vascular media layer. Hepatic profiling of both genetic substrates showed profound differences in expression of contractile proteins that could explain these pathological findings. In summary, the phenotypic presentation of hypertension is associated with multiple processes from vascular bedside to liver as evidenced by nitric oxide production or paraoxonase levels.
Carnicer
Ricardo
R
Departamento de Bioquimica y Biologia Molecular y Celular, Facultad de Veterinaria, Universidad de Zaragoza, Spain.
Guzman
Mario A
MA
Acin
Sergio
S
Surra
Joaquin C
JC
Navarro
Maria A
MA
Arbones-Mainar
Jose M
JM
Arnal
Carmen
C
Morales
Rosa
R
Osada
Jesus
J
D000818:Animals; D016632:Apolipoprotein A-I / Q000172:deficiency*; D001794:Blood Pressure; D002784:Cholesterol / Q000097:blood; D003541:Cystathionine beta-Synthase / Q000172:deficiency*; D005838:Genotype; D006579:Heterozygote; D020138:Hyperhomocysteinemia / Q000235:genetics*; D006973:Hypertension / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000097:blood; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D012313:RNA / Q000235:genetics / Q000302:isolation & purification
D016632:Apolipoprotein A-I; D009569:Nitric Oxide; D012313:RNA; D002784:Cholesterol; D003541:Cystathionine beta-Synthase