Phenotypes associated with this allele

• Allele Symbol: Hdac3^tm1.1Swh
• Allele Name: targeted mutation 1.1, Scott W Heibert
• Allele ID: MGI:3793479
• Summary: 5 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Hdac3^tm1.1Swh/Hdac3^tm1.1Swh	involves: 129S6/SvEvTac * FVB/N	MGI:3795940
cn2	Hdac3^tm1Swh/Hdac3^tm1.1Swh	involves: 129S6/SvEvTac * FVB/N	MGI:3795941
cn3	Hdac3^tm1Swh/Hdac3^tm1.1Swh Tg(Mx1-cre)1Cgn/0	involves: 129S6/SvEvTac * C57BL/6 * CBA	MGI:3795938
cn4	Hdac3^tm1Swh/Hdac3^tm1.1Swh Tg(CAG-cre/Esr1*)5Amc/0	involves: 129S6/SvEvTac * C57BL/6 * CBA * FVB/N	MGI:3795942
cn5	Hdac3^tm1Swh/Hdac3^tm1.1Swh Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129S6/SvEvTac * C57BL/6 * DBA	MGI:3795939

Genotype
MGI:3795940

hm1

• Allelic Composition: Hdac3^tm1.1Swh/Hdac3^tm1.1Swh
• Genetic Background: involves: 129S6/SvEvTac * FVB/N

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

mortality/aging

embryonic lethality, complete penetrance ( J:134665 )

• all embryos are lost before E9.5

Genotype
MGI:3795941

cn2

• Allelic Composition: Hdac3^tm1Swh/Hdac3^tm1.1Swh
• Genetic Background: involves: 129S6/SvEvTac * FVB/N

cellular

abnormal cell physiology ( J:134665 )

• several markers of DNA damage are increased in MEFs at 72 h after adenoviral cre infection

• blocking progression through the cell cycle by serum starving cells reduces the amount of DNA damage detected

• sensitivity to DNA damage by ionizing radiation is also increased in adenoviral cre infected MEFs

abnormal cell cycle ( J:134665 )

• impaired cell cycle progression prior to metaphase in adenoviral cre infected MEFs

• viral cre infected cells display about a 2 h delay in moving from S phase through G2/M and re-entering G1

abnormal cell death ( J:134665 )

• by 120 h post adenoviral cre infection about 20 - 30% of MEFs are dying

decreased cell proliferation ( J:134665 )

• about a 2-fold reduction in BrdU positive MEFs after adenoviral cre infection

Genotype
MGI:3795938

cn3

• Allelic Composition: Hdac3^tm1Swh/Hdac3^tm1.1Swh; Tg(Mx1-cre)1Cgn/0
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * CBA

liver/biliary system

enlarged liver ( J:134288 )

• 2 weeks after the final pIpC injection liver size is increased about 2-fold

• gradual increase in hypertrophic hepatocytes with grainy cytoplasm following pIpC injections

increased liver weight ( J:134288 )

• 2 weeks after the final pIpC injection liver weight is increased about 2-fold

decreased liver glycogen level ( J:134288 )

• dramatic depletion of glycogen in hepatocytes after pIpC injections

abnormal hepatocyte morphology ( J:134288 )

• gradual increase in hypertrophic hepatocytes with grainy cytoplasm following pIpC injections

hepatic steatosis ( J:134288 )

• after pIpC injections

homeostasis/metabolism

decreased liver glycogen level ( J:134288 )

• dramatic depletion of glycogen in hepatocytes after pIpC injections

growth/size/body

enlarged liver ( J:134288 )

• 2 weeks after the final pIpC injection liver size is increased about 2-fold

• gradual increase in hypertrophic hepatocytes with grainy cytoplasm following pIpC injections

increased liver weight ( J:134288 )

• 2 weeks after the final pIpC injection liver weight is increased about 2-fold

Genotype
MGI:3795942

cn4

• Allelic Composition: Hdac3^tm1Swh/Hdac3^tm1.1Swh; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * CBA * FVB/N

cellular

abnormal cell cycle ( J:134665 )

• impaired cell cycle progression prior to metaphase in tamoxifen treated MEFs

increased fibroblast apoptosis ( J:134665 )

• in MEFs following tamoxifen treatment

abnormal DNA repair ( J:134665 )

• several markers of DNA damage are increased in MEFs after tamoxifen treatment

homeostasis/metabolism

abnormal DNA repair ( J:134665 )

• several markers of DNA damage are increased in MEFs after tamoxifen treatment

Genotype
MGI:3795939

cn5

• Allelic Composition: Hdac3^tm1Swh/Hdac3^tm1.1Swh; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * DBA

mortality/aging

mortality/aging ( J:134288 )

N • unlike homozygous null mice, mice with loss of expression in the liver after birth are viable

liver/biliary system

increased hepatocyte proliferation ( J:134288 )

• at 6 - 8 weeks of age, but not at P17, the number of proliferating cells is increased

enlarged liver ( J:134288 )

• by P28 livers are hypertrophic

increased liver weight ( J:134288 )

• ratio of liver weight to body weight is increased to about 25 - 30% compared to about 5% in heterozygous mice

decreased liver glycogen level ( J:134288 )

• dramatic depletion of glycogen in hepatocytes

increased liver triglyceride level ( J:134288 )

• up to a 17-fold increase in triglyceride levels in the liver at P17

abnormal hepatocyte morphology ( J:134288 )

• cells with abnormal cytoplasm are apparent at P17

hepatic steatosis ( J:134288 )

• accumulation of lipid droplets

• elevated triglyceride levels at P17

• treating mice with rapamycin reduces neutral lipid accumulation but does not alter the increase in liver size

pale liver ( J:134288 )

• by P28

homeostasis/metabolism

increased circulating triglyceride level ( J:134288 )

• increases with age

increased circulating alanine transaminase level ( J:134288 )

• by P17

abnormal glucose homeostasis ( J:134288 )

hypoglycemia ( J:134288 )

• present by 6 weeks of age but not at P17

• at 10 weeks of age fasting glucose level is almost 2-fold lower than in control littermates

• however, glucose tolerance is not significantly different from controls

decreased circulating glucagon level ( J:134288 )

• slightly lower at P17

decreased circulating insulin level ( J:134288 )

• dramatic decrease by P28 which persists as mice age

decreased liver glycogen level ( J:134288 )

• dramatic depletion of glycogen in hepatocytes

increased cholesterol level ( J:134288 )

• increases with age

increased circulating cholesterol level ( J:134288 )

• increases with age

increased circulating LDL cholesterol level ( J:134288 )

• increases with age

increased liver triglyceride level ( J:134288 )

• up to a 17-fold increase in triglyceride levels in the liver at P17

growth/size/body

decreased body size ( J:134288 )

• by 4 - 6 weeks of age

enlarged liver ( J:134288 )

• by P28 livers are hypertrophic

increased liver weight ( J:134288 )

• ratio of liver weight to body weight is increased to about 25 - 30% compared to about 5% in heterozygous mice

adipose tissue

decreased total body fat amount ( J:134288 )

• visibly leaner with a substantial reduction in visceral adipose tissue by 6 - 8 weeks of age

cellular

increased hepatocyte proliferation ( J:134288 )

• at 6 - 8 weeks of age, but not at P17, the number of proliferating cells is increased