Identification of a genetic locus on chromosome 11 that regulates leukocyte infiltration in mouse carotid artery.
Arterioscler Thromb Vasc Biol
; 33(5): 1014-9, 2013 May.
Article
en En
| MEDLINE
| ID: mdl-23448970
ABSTRACT
OBJECTIVE:
We demonstrated that inflammatory cells and intima-media thickening are increased in carotids exposed to low-blood flow in the SJL/J (SJL) strain compared with other mouse strains. We hypothesized that the extent of inflammation associated with intima-media thickening is a genetically regulated trait. APPROACH ANDRESULTS:
We performed a whole genome approach to measure leukocyte infiltration in the carotid intima as a quantitative trait in a genetic cross between C3HeB/FeJ (C3H/F) and SJL mice. Immunostaining for CD45(+) (a pan-specific leukocyte marker) was performed on carotids from C3H/F, SJL, F1, and N2 progeny to measure leukocyte infiltration. We identified a nearly significant quantitative trait locus for CD45(+) on chromosome (chr) 11 (17 cM, LOD=2.3; significance was considered at threshold P=0.05). Interval mapping showed that the CD45(+) locus on chr 11 accounted for 8% of the variation in the logarithm of odds backcross. Importantly, the CD45(+) locus colocalized with the intima-modifier 2 (Im2) locus, which controls 17% of intima variation. We created 2 Im2 congenic lines of mice (C3H/F.SJL.11.1 and C3H/F.SJL.11.2) to better understand the regulation of intima-media thickening by the chr 11 locus. The C3H/F.SJL.11.1 congenic mouse showed ≈30% of the SJL trait, confirming that CD45(+) cell infiltration contributed to the intima trait.CONCLUSIONS:
We discovered a novel locus on chr 11 that controls leukocyte infiltration in the carotid. Importantly, this locus overlaps with our previously published Im2 locus on chr 11. Our study reveals a potential mechanistic relationship between leukocyte infiltration and intima-media thickening in response to decreased blood flow.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Arterias Carótidas
/
Túnica Íntima
/
Cromosomas de los Mamíferos
/
Sitios de Carácter Cuantitativo
/
Leucocitos
Tipo de estudio:
Diagnostic_studies
/
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Arterioscler Thromb Vasc Biol
Asunto de la revista:
ANGIOLOGIA
Año:
2013
Tipo del documento:
Article
País de afiliación:
Estados Unidos