Phenotypes Associated with This Genotype

Genotype
MGI:6387277

• Allelic Composition: Bcs1l^tm1.1Levp/Bcs1l^tm1.1Levp
• Genetic Background: B6.129-Bcs1l^tm1.1Levp

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

mortality/aging

premature death ( J:273501 )

• Background Sensitivity: survival on a congenic C57BL/6JCrl background is on average 200 days, longer than on a mixed background

liver/biliary system

abnormal liver morphology ( J:273501 )

• mice on a normal diet exhibit early-stage hepatopathy with expansion of portal triads with incipient fibrosis at P45, and apoptotic cells, single necrotic cells and a proliferative response at P45 which resolves by P95

• liver shows neutral lipid accumulation in mice fed a normal diet

abnormal hepatocyte morphology ( J:273501 )

• mice fed a normal diet exhibit hepatocyte hypertrophy centrivenously and some throughout the lobules

abnormal hepatocyte mitochondrial morphology ( J:273501 )

• hepatocytes show an increase in the proportion of elongated mitochondria in mice fed a normal diet and on the ketogenic diet

• hepatocyte mitochondria exhibit reduced number and increased thickness of cristae in mice fed a normal diet

• the elongated mitochondria in ketogenic-fed mice has a larger cross-sectional area than mitochondria in mutant mice on the normal control diet

abnormal portal triad morphology ( J:273501 )

• mice on a normal diet exhibit expansion of portal triads at P45

• expansion of portal triads resembles hepatic progenitor cell response

• feeding a ketogenic diet prevents portal area expansion

hepatic necrosis ( J:273501 )

• mice fed a normal diet show an increase in necrotic cells in the liver

• feeding a ketogenic diet reduces the number of necrotic cells in the liver

liver fibrosis ( J:273501 )

• mice fed a normal diet exhibit incipient fibrosis at P45 and periportal and sinusoidal fibrosis at P95

• mice fed a normal diet show occasional fibrotic septa connecting two or more portal triads

• mice fed a ketogenic diet show delayed liver fibrosis

abnormal liver physiology ( J:273501 )

• mice fed a normal diet show stellate cell activation

• mice fed a normal diet show an increase in apoptotic cells in the liver

• feeding a ketogenic diet reduces the number of apoptotic cells

liver inflammation ( J:273501 )

• portal inflammation in mice fed a normal diet

cellular

abnormal hepatocyte mitochondrial morphology ( J:273501 )

• hepatocytes show an increase in the proportion of elongated mitochondria in mice fed a normal diet and on the ketogenic diet

• hepatocyte mitochondria exhibit reduced number and increased thickness of cristae in mice fed a normal diet

• the elongated mitochondria in ketogenic-fed mice has a larger cross-sectional area than mitochondria in mutant mice on the normal control diet

abnormal mitochondrial crista morphology ( J:273501 )

• hepatocyte mitochondria exhibit reduced number and increased thickness of cristae in mice fed a normal diet

• feeding a ketogenic diet normalizes the mitochondrial cristae defects

abnormal mitochondrial physiology ( J:273501 )

• mitochondrial respiratory chain complex III (CIII) activity in liver mitochondria is reduced by about 70% on a normal diet

• feeding a ketogenic diet increases CIII activity about 50%

hematopoietic system

increased neutrophil cell number ( J:273501 )

• livers show a marginal increase in neutrophil count in mice fed a normal diet

abnormal macrophage morphology ( J:273501 )

• livers exhibit larger macrophages that protrude out of sinusoids, or multiple macrophages surrounding a hepatocyte

increased macrophage cell number ( J:273501 )

• livers show ceroid- or lipofuscin-laden macrophages in mice fed a normal diet

• feeding a ketogenic diet decreases the number of ceroid- or lipofuscin-laden macrophages

• livers show an increase in the number of IBA1-expressing macrophages at P45 in mice fed a normal diet

• feeding a ketogenic diet normalizes the number of IBA1-expressing macrophages

homeostasis/metabolism

decreased circulating arginine level ( J:273501 )

• plasma level of arginine is decreased in mice fed a normal diet

increased circulating citrulline level ( J:273501 )

• plasma level of citrulline is increased in mice fed a normal diet

increased circulating ornithine level ( J:273501 )

• plasma level of ornithine is increased in mice fed a normal diet

decreased circulating glucose level ( J:273501 )

• non-fasting blood glucose level is lower than in wild-type mice on a normal diet

• however, non-fasting blood glucose level is similar to wild-type mice when fed the ketogenic diet

abnormal enzyme/coenzyme level ( J:273501 )

• citrate synthase activity is increased in livers of mice fed a normal diet and levels are unaffected by the ketogenic diet

increased circulating alanine transaminase level ( J:273501 )

• alanine aminotransferase levels are increased in mice fed a normal diet

increased circulating alkaline phosphatase level ( J:273501 )

• alkaline phosphatase levels are increased in mice fed a normal diet

• feeding a ketogenic diet reduces the levels of alkaline phosphatase

ketosis ( J:273501 )

• mice fed a high-fat, low-carbohydrate ketogenic diet starting at weaning exhibit elevated Beta-hydroxybutyrate levels at P45 and after that, compared to wild-type mice that show an increase at P45 that decreases after this time, indicating persistent ketosis

immune system

increased neutrophil cell number ( J:273501 )

• livers show a marginal increase in neutrophil count in mice fed a normal diet

abnormal macrophage morphology ( J:273501 )

• livers exhibit larger macrophages that protrude out of sinusoids, or multiple macrophages surrounding a hepatocyte

increased macrophage cell number ( J:273501 )

• livers show ceroid- or lipofuscin-laden macrophages in mice fed a normal diet

• feeding a ketogenic diet decreases the number of ceroid- or lipofuscin-laden macrophages

• livers show an increase in the number of IBA1-expressing macrophages at P45 in mice fed a normal diet

• feeding a ketogenic diet normalizes the number of IBA1-expressing macrophages

liver inflammation ( J:273501 )

• portal inflammation in mice fed a normal diet

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
mitochondrial complex III deficiency nuclear type 1		DOID:0080111	OMIM:124000	J:273501