| Gene |
Genome Location (GRCm39) |
Reference |
QTL Note |
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Gdap10 |
Chr12:32874115-32876918 (+) |
J:244215 |
Nonalcoholic fatty liver disease (NAFLD) is a multifactorial disease caused by interactions between environmental and genetic factors.
It was previously determined that SMXA-5 mice develop severe fatty liver on a high fat diet, although parental SM/J and A/J mice were resistant to fatty liver. Quantitative trait analysis using (SM/J x SMxA-5)F2 intercrossed mice identified a significant QTL, Fl1sa (fatty liver 1 in SMXA), for liver weight, liver triglyceride and total lipid content on centromere-53.06 Mb of mouse Chromosome 12. The A/J allele at Fl1sa was associated with the fatty liver. [J:124974] In a subsequent study using the livers from A/J-Chr 12 consomic and A/J mice that were fed a high fat diet three candidate genes were identified, Iah1, Rrm2 and Prkd1 using DNA microarray analysis. [J: 240255]
The goal of the current study was to narrow the previously identified Fl1sa region by genetic dissection using novel congenic mice to identify candidate genes within the narrowed Fl1sa region. Two strains of congenic mice, A.SM-(centromere - D12Mit85)/J (R2) and A.SM-(D12Mit85-D12Mit112)/J (R3), were constructed from parental A/J and A/JChr 12 . Microsatellite markers and SNPs were used for the genotyping of R2 and R3 genomic DNA. Physical positions were taken from GRCm38.P4. The lipid accumulation in the respective livers was analyzed. As the liver triglyceride content in R2 and R3 congenic mice was significantly lower than in A/J mice.
Male A/J, A/J-Chr12, R2 and R3 mice were fed standard chow until 6 weeks of age and thereafter fed a high fat diet from 6 to 13 weeks of age. At 13 weeks of age all mice were sacrificed after a 4 hour fast. The liver and white adipose tissue (subcutaneous fat, epididymal fat, mesenteric fat and retroperitoneal fat) were harvested and weighed. Blood sample were collected to measure serum lipids. Serum triglyceride, cholesterol and hepatic triglyceride content were measured. Whole transcripts from epididymal fats were measured using a Mouse Genome ST 2.0 array.
Liver triglyceride content was significantly lower in A/J-Chr 12, R2 and R3 mice compared with that of A/J mice. Liver triglyceride and liver total lipid in R2 and R3 mice showed intermediate values between those of A/J and A/J-Chr 12 mice. The results suggested that the genes responsible for fatty liver existed in the SM/J region in strain R2 (centromere-29.20 Mb) and in the SM/J region in strain R3 (29.20-46.75 Mb) of Chromosome 12, Fig 1.
Subsequently, in both of the narrowed Fl1sa regions microarray analysis of liver and epididymal fat from A/J and A/J-Chr 12 mice was performed in an attempt to identify candidate genes. Significant differences in gene expression levels in epididymal fat analysis were confirmed in 6 candidate genes: Ntsr2, Zfp125, Gdap10, Nrcam, Stxbp6 and Nova1 between the two strains.
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Iah1 |
Chr12:21366363-21373608 (+) |
J:289414 |
Nonalcoholic fatty liver disease (NAFLD) is a pathological condition caused by excess triglyceride deposition in the liver. The SMXA-5 severe fatty liver mouse model has been established from the SM/J and A/J strains. To explore the genetic factors involved in fatty liver development in SMXA-5 mice, the authors had previously performed QTL analysis, using (SM/JSMXA-5)F2 intercross mice, and identified Fl1sa on Chromosome 12 (centromere-53.06 Mb) as a significant QTL for fatty liver.
Isoamyl acetate-hydrolyzing esterase 1 homolog (Iah1) was selected as the most likely candidate gene for Fl1sa. Iah1 gene expression in fatty liver-resistant A/J-12SM mice was significantly higher than in fatty liver-susceptible A/J mice. These data indicated that the Iah1 gene might be associated with fatty liver development. However, the function of murine Iah1 remains unknown.
Therefore, in this study, the authors created Iah1 knockout (KO) mice with two different backgrounds [C57BL/6N (B6) and A/J-12SM (A12)] to investigate the relationship between Iah1 and liver lipid accumulation. Liver triglyceride accumulation in Iah1-KO mice of B6 or A12 background did not differ from their respective Iah1-wild type mice under a high-fat diet. These results indicated that loss of Iah1 did not contribute to fatty liver.
On the other hand, adipose tissue dysfunction causes lipid accumulation in ectopic tissues (liver, skeletal muscle, and pancreas). To investigate the effect of Iah1 deficiency on white adipose tissue, the authors performed DNA microarray analysis of epididymal fat in Iah1-KO mice of A12 background. This result showed that Iah1 deficiency might decrease adipokines Sfrp4 and Metrnl gene expression in epididymal fat.
This study demonstrated that Iah1 deficiency did not cause liver lipid accumulation and that Iah1 was not a suitable candidate gene for Fl1sa. |
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Iah1 |
Chr12:21366363-21373608 (+) |
J:240255 |
The SMXA-5 mouse is an animal model of high-fat diet-induced fatty liver. The major QTL for fatty liver, Fl1sa on chromosome 12, was previously identified in a SM/J SMXA-5 intercross. The SMXA-5 genome consists of the SM/J and A/J genomes, and the A/J allele of Fl1sa is the fatty liver-susceptibility allele. The existence of the responsible genes for fatty liver within Fl1sa was confirmed in A/J-Chr 12 consomic mice. [J:124974].
The aim of the current study was to identify candidate genes for Fl1sa, and to investigate whether the identified genes affect the lipid metabolism.
To identify candidate genes for Fl1sa, DNA microarray analysis was performed using the livers of A/J-Chr 12 and A/J mice that were fed a high-fat diet. The mRNA levels of three genes (Iah1, Rrm2, Prkd1) in the chromosomal region of Fl1sa were significantly different between the strains.
Iah1 mRNA levels in the liver, kidney, and lung were significantly higher in
A/J-Chr 12 mice than in A/J mice. The hepatic Iah1 mRNA level in A/J-Chr 12 mice was 3.2-fold higher than that in A/J mice. A stable cell line expressing the mouse Iah1 protein in mouse hepatoma Hepa1-6 cells was constructed. Overexpression of Iah1 in Hepa1-6 cells suppressed the mRNA levels of Cd36 and Dgat2, genes which play important roles in triglyceride synthesis and lipid metabolism.
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Nova1 |
Chr12:46744678-46866143 (-) |
J:244215 |
Nonalcoholic fatty liver disease (NAFLD) is a multifactorial disease caused by interactions between environmental and genetic factors.
It was previously determined that SMXA-5 mice develop severe fatty liver on a high fat diet, although parental SM/J and A/J mice were resistant to fatty liver. Quantitative trait analysis using (SM/J x SMxA-5)F2 intercrossed mice identified a significant QTL, Fl1sa (fatty liver 1 in SMXA), for liver weight, liver triglyceride and total lipid content on centromere-53.06 Mb of mouse Chromosome 12. The A/J allele at Fl1sa was associated with the fatty liver. [J:124974] In a subsequent study using the livers from A/J-Chr 12 consomic and A/J mice that were fed a high fat diet three candidate genes were identified, Iah1, Rrm2 and Prkd1 using DNA microarray analysis. [J: 240255]
The goal of the current study was to narrow the previously identified Fl1sa region by genetic dissection using novel congenic mice to identify candidate genes within the narrowed Fl1sa region. Two strains of congenic mice, A.SM-(centromere - D12Mit85)/J (R2) and A.SM-(D12Mit85-D12Mit112)/J (R3), were constructed from parental A/J and A/JChr 12 . Microsatellite markers and SNPs were used for the genotyping of R2 and R3 genomic DNA. Physical positions were taken from GRCm38.P4. The lipid accumulation in the respective livers was analyzed. As the liver triglyceride content in R2 and R3 congenic mice was significantly lower than in A/J mice.
Male A/J, A/J-Chr12, R2 and R3 mice were fed standard chow until 6 weeks of age and thereafter fed a high fat diet from 6 to 13 weeks of age. At 13 weeks of age all mice were sacrificed after a 4 hour fast. The liver and white adipose tissue (subcutaneous fat, epididymal fat, mesenteric fat and retroperitoneal fat) were harvested and weighed. Blood sample were collected to measure serum lipids. Serum triglyceride, cholesterol and hepatic triglyceride content were measured. Whole transcripts from epididymal fats were measured using a Mouse Genome ST 2.0 array.
Liver triglyceride content was significantly lower in A/J-Chr 12, R2 and R3 mice compared with that of A/J mice. Liver triglyceride and liver total lipid in R2 and R3 mice showed intermediate values between those of A/J and A/J-Chr 12 mice. The results suggested that the genes responsible for fatty liver existed in the SM/J region in strain R2 (centromere-29.20 Mb) and in the SM/J region in strain R3 (29.20-46.75 Mb) of Chromosome 12, Fig 1.
Subsequently, in both of the narrowed Fl1sa regions microarray analysis of liver and epididymal fat from A/J and A/J-Chr 12 mice was performed in an attempt to identify candidate genes. Significant differences in gene expression levels in epididymal fat analysis were confirmed in 6 candidate genes: Ntsr2, Zfp125, Gdap10, Nrcam, Stxbp6 and Nova1 between the two strains.
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Nrcam |
Chr12:44375668-44648747 (+) |
J:244215 |
Nonalcoholic fatty liver disease (NAFLD) is a multifactorial disease caused by interactions between environmental and genetic factors.
It was previously determined that SMXA-5 mice develop severe fatty liver on a high fat diet, although parental SM/J and A/J mice were resistant to fatty liver. Quantitative trait analysis using (SM/J x SMxA-5)F2 intercrossed mice identified a significant QTL, Fl1sa (fatty liver 1 in SMXA), for liver weight, liver triglyceride and total lipid content on centromere-53.06 Mb of mouse Chromosome 12. The A/J allele at Fl1sa was associated with the fatty liver. [J:124974] In a subsequent study using the livers from A/J-Chr 12 consomic and A/J mice that were fed a high fat diet three candidate genes were identified, Iah1, Rrm2 and Prkd1 using DNA microarray analysis. [J: 240255]
The goal of the current study was to narrow the previously identified Fl1sa region by genetic dissection using novel congenic mice to identify candidate genes within the narrowed Fl1sa region. Two strains of congenic mice, A.SM-(centromere - D12Mit85)/J (R2) and A.SM-(D12Mit85-D12Mit112)/J (R3), were constructed from parental A/J and A/JChr 12 . Microsatellite markers and SNPs were used for the genotyping of R2 and R3 genomic DNA. Physical positions were taken from GRCm38.P4. The lipid accumulation in the respective livers was analyzed. As the liver triglyceride content in R2 and R3 congenic mice was significantly lower than in A/J mice.
Male A/J, A/J-Chr12, R2 and R3 mice were fed standard chow until 6 weeks of age and thereafter fed a high fat diet from 6 to 13 weeks of age. At 13 weeks of age all mice were sacrificed after a 4 hour fast. The liver and white adipose tissue (subcutaneous fat, epididymal fat, mesenteric fat and retroperitoneal fat) were harvested and weighed. Blood sample were collected to measure serum lipids. Serum triglyceride, cholesterol and hepatic triglyceride content were measured. Whole transcripts from epididymal fats were measured using a Mouse Genome ST 2.0 array.
Liver triglyceride content was significantly lower in A/J-Chr 12, R2 and R3 mice compared with that of A/J mice. Liver triglyceride and liver total lipid in R2 and R3 mice showed intermediate values between those of A/J and A/J-Chr 12 mice. The results suggested that the genes responsible for fatty liver existed in the SM/J region in strain R2 (centromere-29.20 Mb) and in the SM/J region in strain R3 (29.20-46.75 Mb) of Chromosome 12, Fig 1.
Subsequently, in both of the narrowed Fl1sa regions microarray analysis of liver and epididymal fat from A/J and A/J-Chr 12 mice was performed in an attempt to identify candidate genes. Significant differences in gene expression levels in epididymal fat analysis were confirmed in 6 candidate genes: Ntsr2, Zfp125, Gdap10, Nrcam, Stxbp6 and Nova1 between the two strains.
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|
Ntsr2 |
Chr12:16703477-16710223 (+) |
J:244215 |
Nonalcoholic fatty liver disease (NAFLD) is a multifactorial disease caused by interactions between environmental and genetic factors.
It was previously determined that SMXA-5 mice develop severe fatty liver on a high fat diet, although parental SM/J and A/J mice were resistant to fatty liver. Quantitative trait analysis using (SM/J x SMxA-5)F2 intercrossed mice identified a significant QTL, Fl1sa (fatty liver 1 in SMXA), for liver weight, liver triglyceride and total lipid content on centromere-53.06 Mb of mouse Chromosome 12. The A/J allele at Fl1sa was associated with the fatty liver. [J:124974] In a subsequent study using the livers from A/J-Chr 12 consomic and A/J mice that were fed a high fat diet three candidate genes were identified, Iah1, Rrm2 and Prkd1 using DNA microarray analysis. [J: 240255]
The goal of the current study was to narrow the previously identified Fl1sa region by genetic dissection using novel congenic mice to identify candidate genes within the narrowed Fl1sa region. Two strains of congenic mice, A.SM-(centromere - D12Mit85)/J (R2) and A.SM-(D12Mit85-D12Mit112)/J (R3), were constructed from parental A/J and A/JChr 12 . Microsatellite markers and SNPs were used for the genotyping of R2 and R3 genomic DNA. Physical positions were taken from GRCm38.P4. The lipid accumulation in the respective livers was analyzed. As the liver triglyceride content in R2 and R3 congenic mice was significantly lower than in A/J mice.
Male A/J, A/J-Chr12, R2 and R3 mice were fed standard chow until 6 weeks of age and thereafter fed a high fat diet from 6 to 13 weeks of age. At 13 weeks of age all mice were sacrificed after a 4 hour fast. The liver and white adipose tissue (subcutaneous fat, epididymal fat, mesenteric fat and retroperitoneal fat) were harvested and weighed. Blood sample were collected to measure serum lipids. Serum triglyceride, cholesterol and hepatic triglyceride content were measured. Whole transcripts from epididymal fats were measured using a Mouse Genome ST 2.0 array.
Liver triglyceride content was significantly lower in A/J-Chr 12, R2 and R3 mice compared with that of A/J mice. Liver triglyceride and liver total lipid in R2 and R3 mice showed intermediate values between those of A/J and A/J-Chr 12 mice. The results suggested that the genes responsible for fatty liver existed in the SM/J region in strain R2 (centromere-29.20 Mb) and in the SM/J region in strain R3 (29.20-46.75 Mb) of Chromosome 12, Fig 1.
Subsequently, in both of the narrowed Fl1sa regions microarray analysis of liver and epididymal fat from A/J and A/J-Chr 12 mice was performed in an attempt to identify candidate genes. Significant differences in gene expression levels in epididymal fat analysis were confirmed in 6 candidate genes: Ntsr2, Zfp125, Gdap10, Nrcam, Stxbp6 and Nova1 between the two strains.
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Prkd1 |
Chr12:50388014-50695881 (-) |
J:240255 |
The SMXA-5 mouse is an animal model of high-fat diet-induced fatty liver. The major QTL for fatty liver, Fl1sa on chromosome 12, was previously identified in a SM/J SMXA-5 intercross. The SMXA-5 genome consists of the SM/J and A/J genomes, and the A/J allele of Fl1sa is the fatty liver-susceptibility allele. The existence of the responsible genes for fatty liver within Fl1sa was confirmed in A/J-Chr 12 consomic mice. [J:124974].
The aim of the current study was to identify candidate genes for Fl1sa, and to investigate whether the identified genes affect the lipid metabolism.
To identify candidate genes for Fl1sa, DNA microarray analysis was performed using the livers of A/J-Chr 12 and A/J mice that were fed a high-fat diet. The mRNA levels of three genes (Iah1, Rrm2, Prkd1) in the chromosomal region of Fl1sa were significantly different between the strains.
Iah1 mRNA levels in the liver, kidney, and lung were significantly higher in
A/J-Chr 12 mice than in A/J mice. The hepatic Iah1 mRNA level in A/J-Chr 12 mice was 3.2-fold higher than that in A/J mice. A stable cell line expressing the mouse Iah1 protein in mouse hepatoma Hepa1-6 cells was constructed. Overexpression of Iah1 in Hepa1-6 cells suppressed the mRNA levels of Cd36 and Dgat2, genes which play important roles in triglyceride synthesis and lipid metabolism.
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Rrm2 |
Chr12:24758253-24764145 (+) |
J:240255 |
The SMXA-5 mouse is an animal model of high-fat diet-induced fatty liver. The major QTL for fatty liver, Fl1sa on chromosome 12, was previously identified in a SM/J SMXA-5 intercross. The SMXA-5 genome consists of the SM/J and A/J genomes, and the A/J allele of Fl1sa is the fatty liver-susceptibility allele. The existence of the responsible genes for fatty liver within Fl1sa was confirmed in A/J-Chr 12 consomic mice. [J:124974].
The aim of the current study was to identify candidate genes for Fl1sa, and to investigate whether the identified genes affect the lipid metabolism.
To identify candidate genes for Fl1sa, DNA microarray analysis was performed using the livers of A/J-Chr 12 and A/J mice that were fed a high-fat diet. The mRNA levels of three genes (Iah1, Rrm2, Prkd1) in the chromosomal region of Fl1sa were significantly different between the strains.
Iah1 mRNA levels in the liver, kidney, and lung were significantly higher in
A/J-Chr 12 mice than in A/J mice. The hepatic Iah1 mRNA level in A/J-Chr 12 mice was 3.2-fold higher than that in A/J mice. A stable cell line expressing the mouse Iah1 protein in mouse hepatoma Hepa1-6 cells was constructed. Overexpression of Iah1 in Hepa1-6 cells suppressed the mRNA levels of Cd36 and Dgat2, genes which play important roles in triglyceride synthesis and lipid metabolism.
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Stxbp6 |
Chr12:44899267-45121248 (-) |
J:244215 |
Nonalcoholic fatty liver disease (NAFLD) is a multifactorial disease caused by interactions between environmental and genetic factors.
It was previously determined that SMXA-5 mice develop severe fatty liver on a high fat diet, although parental SM/J and A/J mice were resistant to fatty liver. Quantitative trait analysis using (SM/J x SMxA-5)F2 intercrossed mice identified a significant QTL, Fl1sa (fatty liver 1 in SMXA), for liver weight, liver triglyceride and total lipid content on centromere-53.06 Mb of mouse Chromosome 12. The A/J allele at Fl1sa was associated with the fatty liver. [J:124974] In a subsequent study using the livers from A/J-Chr 12 consomic and A/J mice that were fed a high fat diet three candidate genes were identified, Iah1, Rrm2 and Prkd1 using DNA microarray analysis. [J: 240255]
The goal of the current study was to narrow the previously identified Fl1sa region by genetic dissection using novel congenic mice to identify candidate genes within the narrowed Fl1sa region. Two strains of congenic mice, A.SM-(centromere - D12Mit85)/J (R2) and A.SM-(D12Mit85-D12Mit112)/J (R3), were constructed from parental A/J and A/JChr 12 . Microsatellite markers and SNPs were used for the genotyping of R2 and R3 genomic DNA. Physical positions were taken from GRCm38.P4. The lipid accumulation in the respective livers was analyzed. As the liver triglyceride content in R2 and R3 congenic mice was significantly lower than in A/J mice.
Male A/J, A/J-Chr12, R2 and R3 mice were fed standard chow until 6 weeks of age and thereafter fed a high fat diet from 6 to 13 weeks of age. At 13 weeks of age all mice were sacrificed after a 4 hour fast. The liver and white adipose tissue (subcutaneous fat, epididymal fat, mesenteric fat and retroperitoneal fat) were harvested and weighed. Blood sample were collected to measure serum lipids. Serum triglyceride, cholesterol and hepatic triglyceride content were measured. Whole transcripts from epididymal fats were measured using a Mouse Genome ST 2.0 array.
Liver triglyceride content was significantly lower in A/J-Chr 12, R2 and R3 mice compared with that of A/J mice. Liver triglyceride and liver total lipid in R2 and R3 mice showed intermediate values between those of A/J and A/J-Chr 12 mice. The results suggested that the genes responsible for fatty liver existed in the SM/J region in strain R2 (centromere-29.20 Mb) and in the SM/J region in strain R3 (29.20-46.75 Mb) of Chromosome 12, Fig 1.
Subsequently, in both of the narrowed Fl1sa regions microarray analysis of liver and epididymal fat from A/J and A/J-Chr 12 mice was performed in an attempt to identify candidate genes. Significant differences in gene expression levels in epididymal fat analysis were confirmed in 6 candidate genes: Ntsr2, Zfp125, Gdap10, Nrcam, Stxbp6 and Nova1 between the two strains.
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Zfp125 |
Chr12:20948575-20952660 (-) |
J:244215 |
Nonalcoholic fatty liver disease (NAFLD) is a multifactorial disease caused by interactions between environmental and genetic factors.
It was previously determined that SMXA-5 mice develop severe fatty liver on a high fat diet, although parental SM/J and A/J mice were resistant to fatty liver. Quantitative trait analysis using (SM/J x SMxA-5)F2 intercrossed mice identified a significant QTL, Fl1sa (fatty liver 1 in SMXA), for liver weight, liver triglyceride and total lipid content on centromere-53.06 Mb of mouse Chromosome 12. The A/J allele at Fl1sa was associated with the fatty liver. [J:124974] In a subsequent study using the livers from A/J-Chr 12 consomic and A/J mice that were fed a high fat diet three candidate genes were identified, Iah1, Rrm2 and Prkd1 using DNA microarray analysis. [J: 240255]
The goal of the current study was to narrow the previously identified Fl1sa region by genetic dissection using novel congenic mice to identify candidate genes within the narrowed Fl1sa region. Two strains of congenic mice, A.SM-(centromere - D12Mit85)/J (R2) and A.SM-(D12Mit85-D12Mit112)/J (R3), were constructed from parental A/J and A/JChr 12 . Microsatellite markers and SNPs were used for the genotyping of R2 and R3 genomic DNA. Physical positions were taken from GRCm38.P4. The lipid accumulation in the respective livers was analyzed. As the liver triglyceride content in R2 and R3 congenic mice was significantly lower than in A/J mice.
Male A/J, A/J-Chr12, R2 and R3 mice were fed standard chow until 6 weeks of age and thereafter fed a high fat diet from 6 to 13 weeks of age. At 13 weeks of age all mice were sacrificed after a 4 hour fast. The liver and white adipose tissue (subcutaneous fat, epididymal fat, mesenteric fat and retroperitoneal fat) were harvested and weighed. Blood sample were collected to measure serum lipids. Serum triglyceride, cholesterol and hepatic triglyceride content were measured. Whole transcripts from epididymal fats were measured using a Mouse Genome ST 2.0 array.
Liver triglyceride content was significantly lower in A/J-Chr 12, R2 and R3 mice compared with that of A/J mice. Liver triglyceride and liver total lipid in R2 and R3 mice showed intermediate values between those of A/J and A/J-Chr 12 mice. The results suggested that the genes responsible for fatty liver existed in the SM/J region in strain R2 (centromere-29.20 Mb) and in the SM/J region in strain R3 (29.20-46.75 Mb) of Chromosome 12, Fig 1.
Subsequently, in both of the narrowed Fl1sa regions microarray analysis of liver and epididymal fat from A/J and A/J-Chr 12 mice was performed in an attempt to identify candidate genes. Significant differences in gene expression levels in epididymal fat analysis were confirmed in 6 candidate genes: Ntsr2, Zfp125, Gdap10, Nrcam, Stxbp6 and Nova1 between the two strains.
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