HLBS Phenotypic Deviant Report

HLB # 301
MGI Accession # MGI:2683059
Mouse Identifier 35367
Date Mouse Born 11/15/2002
Sex Female
Genetic Background C57BL/6J
Mutagen ENU (See ENU Treatment Protocol)
Phenotype Index Hypercholesterolemia
Phenotype Description While the absolute value for total Cholesterol (377 mg/dl) at 13 weeks of age, after consuming the atherogenic diet for >5 weeks, is within normal range for C57BL/6J, this animal started out with a 4 hour fasted plasma total Cholesterol of 88 mg/dl, resulting in a 415% increase, which is greater than the controls. See the baseline comparison data for C57BL/6J in the Mouse Phenome Database.

Mice from this line look healthy, and very much like background strain
C57BL/6J.  They breed well, even after 5 weeks on the atherogenic diet.
Other information

Two affected siblings (HLB299 & HLB300), and same G1 father as 245.

Other details about this animal line and environment:

  1. This line is housed in an SPF facility
  2. Total cholesterol is elevated >5 fold in response to short challenge with an atherogenic diet (2-3 fold in B6)
    Chow: 90 mg/dl (2.3 S.I.) (50-150; 1.3-3.9)
    HF (5 weeks): 400-2000 mg/dl (10.4-51.8) (75-350; 1.9-9.1)
  3. Baseline (chow) cholesterol, HDL normal
  4. HDL is elevated >2 fold on ath diet (not in B6)
    Chow: 60 mg/dl (1.6) (50-90)
    HF (5 weeks):  100-400 mg/dl (2.6-10.4) (40-100)
  5. Severe atherosclerosis (aorta, coronary and pulmonary arteries)
  6. Cholesterol, HDL remain high 1 month after resuming chow diet
  7. Cholesterol gallstones in 50%
  8. No obesity; no skin xanthomas

The slides above on the left show qualitative advanced lesions in the aorta:  Trichrome staining reveals the presence of collagen and progression to fibrous plaque. The slides on the right show early coronary and pulmonary lesions, and subendothelial accumulation of lipid-laden macrophages (foam cells).

The slide below captures quantitative lesion measurement in the aortic root at valve. The oil red 0 stained region exhibits lesion size of 590105 µm2. This particular animal had a baseline cholesterol of 222mg/dl; baseline HDL of 93 mg/dl. After 5 weeks on the high fat diet, cholesterol was 1365 mg/dl; and HDL was 270 mg/dl.
Heritability The heritability of the phenotype has been confirmed.
Chromosome Mapped x strain DBA2/J to chromosome 9. Click here to view a poster describing this apparent coisogenic LDLr mutation.
Inheritance Semi-dominant
Molecular Interval = low-density lipoprotein receptor @ 21.6 Bm (5 cM)
Date Posted 10/28/03
Availability Currently available for distribution as cryopreserved homozygous embryos.

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Supported by the National Heart, Lung, and Blood Institute (NHLBI) (Grant # HL66611)