Phenotypes associated with this allele

• Allele Symbol: Hdac3^tm1.1Eno
• Allele Name: targeted mutation 1.1, Eric N Olson
• Allele ID: MGI:3831693
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Hdac3^tm1.1Eno/Hdac3^tm1.1Eno Pgr^tm2(cre)Lyd/Pgr^+	involves: 129S/SvEv * 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:6281662
cn2	Hdac3^tm1.1Eno/Hdac3^tm1.1Eno Tg(Myh6-cre)2182Mds/?	involves: 129S/SvEv * C57BL/6	MGI:3831703

Genotype
MGI:6281662

cn1

• Allelic Composition: Hdac3^tm1.1Eno/Hdac3^tm1.1Eno; Pgr^tm2(cre)Lyd/Pgr⁺
• Genetic Background: involves: 129S/SvEv * 129S1/Sv * 129X1/SvJ * C57BL/6

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

reproductive system

reproductive system phenotype ( J:269518 )

♀N • females exhibit normal ovulation, fertilization, and ovarian histology relative to control mice

abnormal decidualization ( J:269518 )

♀ • at day 5.5 of gestation (GD 5.5), embryos are free-floating within the uterine lumen and no decidual cells are observed, unlike in control uteri

♀ • following artificially induced decidualization, the ratio of uterine weight to body weight is significantly lower than that in control mice, indicating a decidual defect; mRNA expression of decidualization marker genes Wnt4 and Bmp2 is significantly reduced in the uterus

abnormal endometrium morphology ( J:269518 )

♀ • at GD 3.5, the expression of stromal markers vimentin and COUP-TFII is significantly reduced in endometrial stromal cells

endometrium fibrosis ( J:269518 )

♀ • immunohistochemical staining showed significantly increased collagen type I protein levels in endometrial stromal cells at GD 3.5, suggesting that endometrial stroma is largely replaced by fibrous tissue

abnormal embryo attachment ( J:269518 )

♀ • at GD 5.5, embryos are free-floating within the uterine lumen, unlike in control uteri

failure of embryo implantation ( J:269518 )

♀ • no implantation sites are detected in the uterine horns at GD 5.5

abnormal uterine receptivity ( J:269518 )

♀

abnormal uterus physiology ( J:269518 )

♀ • at GD 3.5, Ki-67 staining revealed significantly altered proliferative responses in the uterine stromal and epithelial compartments: the % of Ki-67+ endometrial epithelial cells is increased whereas the % of Ki-67+ stromal cells is decreased, unlike in control uteri

♀ • expression of estrogen receptor 1 alpha (ESR1) and progesterone receptor (PGR) is significantly reduced in endometrial stromal cells at GD 3.5, indicating decreased progesterone signaling

female infertility ( J:269518 )

♀ • adult females are completely sterile primarily due to a uterine defect

embryo

abnormal decidualization ( J:269518 )

♀ • at day 5.5 of gestation (GD 5.5), embryos are free-floating within the uterine lumen and no decidual cells are observed, unlike in control uteri

♀ • following artificially induced decidualization, the ratio of uterine weight to body weight is significantly lower than that in control mice, indicating a decidual defect; mRNA expression of decidualization marker genes Wnt4 and Bmp2 is significantly reduced in the uterus

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:269518 )

♀N • at GD 3.5, females exhibit normal serum progesterone and estrogen levels relative to control mice

increased collagen level ( J:269518 )

♀ • H&E and Massons trichrome staining revealed increased collagen levels in uterine stromal cells starting at 6 weeks of age

♀ • immunohistochemical staining showed significantly increased collagen type I protein levels in endometrial stromal cells at GD 3.5

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
endometriosis		DOID:289		J:269518

Genotype
MGI:3831703

cn2

• Allelic Composition: Hdac3^tm1.1Eno/Hdac3^tm1.1Eno; Tg(Myh6-cre)2182Mds/?
• Genetic Background: involves: 129S/SvEv * C57BL/6

growth/size/body

increased heart weight ( J:144604 )

• 72% increase in heart weight/body weight ratio by 12 weeks of age

cardiac hypertrophy ( J:144604 )

• signs of cardiac hypertrophy by 4 weeks of age

• hypertrophy exacerbated by 12 weeks of age

• both right and left atria are enlarged

• cardiomyocyte hypertrophy, particularly in the left ventricle free wall and the septum

mortality/aging

premature death ( J:144604 )

• significant lethality between 12 and 14 weeks of age

• 100% lethality by 16 weeks

cardiovascular system

cardiovascular system phenotype ( J:144604 )

N • normal sinus rhythm

increased cardiac muscle triglyceride level ( J:144604 )

• fasting myocardial triglycerides are increased after 24 hours

abnormal heart morphology ( J:144604 )

abnormal myocardial fiber mitochondrial morphology ( J:144604 )

• lack normal association with sarcomeres in cardiac muscle

abnormal heart size ( J:144604 )

increased heart weight ( J:144604 )

• 72% increase in heart weight/body weight ratio by 12 weeks of age

cardiac hypertrophy ( J:144604 )

• signs of cardiac hypertrophy by 4 weeks of age

• hypertrophy exacerbated by 12 weeks of age

• both right and left atria are enlarged

• cardiomyocyte hypertrophy, particularly in the left ventricle free wall and the septum

dilated heart left ventricle ( J:144604 )

• increased in both systole and diastole

cardiac interstitial fibrosis ( J:144604 )

decreased ventricle muscle contractility ( J:144604 )

• reduced fractional shortening of the left ventricle

cellular

abnormal myocardial fiber mitochondrial morphology ( J:144604 )

• lack normal association with sarcomeres in cardiac muscle

cardiac interstitial fibrosis ( J:144604 )

abnormal mitochondrial crista morphology ( J:144604 )

• reduced density of cristae

abnormal cellular respiration ( J:144604 )

• 25% reduction in complex I activity

• 39% reduction in NADH oxidase activity

• two fold increase in free radical production

homeostasis/metabolism

abnormal lipid level ( J:144604 )

• accumulation of neutral lipids in ventricles but not atria

increased cardiac muscle triglyceride level ( J:144604 )

• fasting myocardial triglycerides are increased after 24 hours

muscle

increased cardiac muscle triglyceride level ( J:144604 )

• fasting myocardial triglycerides are increased after 24 hours

abnormal myocardial fiber mitochondrial morphology ( J:144604 )

• lack normal association with sarcomeres in cardiac muscle

decreased ventricle muscle contractility ( J:144604 )

• reduced fractional shortening of the left ventricle