Phenotypes associated with this allele

• Allele Symbol: Hand2^tm1Cse
• Allele Name: targeted mutation 1, Peter Cserjesi
• Allele ID: MGI:3715149
• Summary: 9 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
ht1	Hand2^tm1Cse/Hand2^tm1Dsr	involves: 129S1/Sv * 129S7/SvEvBrd * C57BL/6	MGI:3715253
cn2	Hand2^tm1Cse/Hand2^+ Tg(DBH-cre)1Cse/0	involves: 129S1/Sv	MGI:4417973
cn3	Hand2^tm1Cse/Hand2^tm1Cse Tg(Pitx2-cre)1Ych/0	involves: 129S1/Sv * 129S7/SvEvBrd * C57BL/6	MGI:3848963
cn4	Hand2^tm1Cse/Hand2^tm1Cse Osr2^tm2(cre)Jian/Osr2^+	involves: 129S1/Sv * 129S7/SvEvBrd * C57BL/6	MGI:3848961
cn5	Hand2^tm1Cse/Hand2^tm1Cse H2az2^Tg(Wnt1-cre)11Rth/H2az2^+	involves: 129S1/Sv * 129S7/SvEvBrd * C57BL/6 * CBA	MGI:3715254
cn6	Hand2^tm1Cse/Hand2^tm1Dsr H2az2^Tg(Wnt1-cre)11Rth/H2az2^+	involves: 129S1/Sv * 129S7/SvEvBrd * C57BL/6 * CBA	MGI:3848967
cn7	Hand2^tm1Cse/Hand2^+ H2az2^Tg(Wnt1-cre)11Rth/H2az2^+	involves: 129S1/Sv * C57BL/6J * CBA/J	MGI:4417976
cn8	Hand2^tm1Cse/Hand2^+ Tg(Tnnt2-cre)5Blh/0	involves: 129S1/Sv * C57BL/6J * DBA/2	MGI:4417974
cn9	Hand2^tm1Cse/Hand2^+ Tg(Hoxb6-cre)#Mku/0	involves: 129S1/Sv * FVB/N	MGI:4417975

Genotype
MGI:3715253

ht1

• Allelic Composition: Hand2^tm1Cse/Hand2^tm1Dsr
• Genetic Background: involves: 129S1/Sv * 129S7/SvEvBrd * C57BL/6

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

mortality/aging

neonatal lethality, complete penetrance ( J:122604 )

• pups die within a day of birth with cleft palates

behavior/neurological

abnormal suckling behavior ( J:122604 )

• newborn pups cannot feed

craniofacial

abnormal primary and secondary palatal fusion ( J:122604 )

• the primary palate forms, but growth is incomplete and primary palates fails to fuse with secondary palate

palatal shelves fail to meet at midline ( J:149232 )

• at E15.5 palatal shelves have elevated to the horizontal level, but appear short and misaligned and the posterior area of palate has not elevated

• excessive apoptosis of periderm cells of the surface epithelium is observed in medial edge epithelium (MEE); basal layer epithelial cells do not show increased apoptosis

decreased palatal shelf size ( J:149232 )

• at E13.5, shelves are positioned normally, but appear slightly smaller than controls

cleft secondary palate ( J:122604 )

• the secondary palate contains a wide cleft in the anterior and mid-section

abnormal palatal shelf elevation ( J:149232 )

• at E14.4, palatal shelves fail to elevate and remain in a vertical position at sides of tongue

• at E15.5 palatal shelves have elevated to the horizontal level, but appear short and misaligned and the posterior area of palate has not elevated

tongue hypoplasia ( J:149232 )

• tongue is hypoplastic at E14.5

digestive/alimentary system

abnormal primary and secondary palatal fusion ( J:122604 )

• the primary palate forms, but growth is incomplete and primary palates fails to fuse with secondary palate

palatal shelves fail to meet at midline ( J:149232 )

• at E15.5 palatal shelves have elevated to the horizontal level, but appear short and misaligned and the posterior area of palate has not elevated

• excessive apoptosis of periderm cells of the surface epithelium is observed in medial edge epithelium (MEE); basal layer epithelial cells do not show increased apoptosis

decreased palatal shelf size ( J:149232 )

• at E13.5, shelves are positioned normally, but appear slightly smaller than controls

cleft secondary palate ( J:122604 )

• the secondary palate contains a wide cleft in the anterior and mid-section

abnormal palatal shelf elevation ( J:149232 )

• at E14.4, palatal shelves fail to elevate and remain in a vertical position at sides of tongue

• at E15.5 palatal shelves have elevated to the horizontal level, but appear short and misaligned and the posterior area of palate has not elevated

tongue hypoplasia ( J:149232 )

• tongue is hypoplastic at E14.5

growth/size/body

abnormal primary and secondary palatal fusion ( J:122604 )

• the primary palate forms, but growth is incomplete and primary palates fails to fuse with secondary palate

palatal shelves fail to meet at midline ( J:149232 )

• at E15.5 palatal shelves have elevated to the horizontal level, but appear short and misaligned and the posterior area of palate has not elevated

• excessive apoptosis of periderm cells of the surface epithelium is observed in medial edge epithelium (MEE); basal layer epithelial cells do not show increased apoptosis

decreased palatal shelf size ( J:149232 )

• at E13.5, shelves are positioned normally, but appear slightly smaller than controls

cleft secondary palate ( J:122604 )

• the secondary palate contains a wide cleft in the anterior and mid-section

abnormal palatal shelf elevation ( J:149232 )

• at E14.4, palatal shelves fail to elevate and remain in a vertical position at sides of tongue

• at E15.5 palatal shelves have elevated to the horizontal level, but appear short and misaligned and the posterior area of palate has not elevated

tongue hypoplasia ( J:149232 )

• tongue is hypoplastic at E14.5

Genotype
MGI:4417973

cn2

• Allelic Composition: Hand2^tm1Cse/Hand2⁺; Tg(DBH-cre)1Cse/0
• Genetic Background: involves: 129S1/Sv

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:155265 )

• no viable embryos are recovered past 12.5 dpc

cardiovascular system

visceral vascular congestion ( J:155265 )

• all embryos collected at 12.5 dpc exhibit pooling of blood in the liver and peripheral vasculature

liver vascular congestion ( J:155265 )

liver/biliary system

liver vascular congestion ( J:155265 )

Genotype
MGI:3848963

cn3

• Allelic Composition: Hand2^tm1Cse/Hand2^tm1Cse; Tg(Pitx2-cre)1Ych/0
• Genetic Background: involves: 129S1/Sv * 129S7/SvEvBrd * C57BL/6

craniofacial

cleft secondary palate ( J:149232 )

• a wide open cleft palate is observed

• no aberrant apoptosis is detected in palatal epithelium at E13.5

failure of palatal shelf elevation ( J:149232 )

• palatal shelves are not elevated at E16.5 (Fig. 4e)

digestive/alimentary system

cleft secondary palate ( J:149232 )

• a wide open cleft palate is observed

• no aberrant apoptosis is detected in palatal epithelium at E13.5

failure of palatal shelf elevation ( J:149232 )

• palatal shelves are not elevated at E16.5 (Fig. 4e)

growth/size/body

cleft secondary palate ( J:149232 )

• a wide open cleft palate is observed

• no aberrant apoptosis is detected in palatal epithelium at E13.5

failure of palatal shelf elevation ( J:149232 )

• palatal shelves are not elevated at E16.5 (Fig. 4e)

Genotype
MGI:3848961

cn4

• Allelic Composition: Hand2^tm1Cse/Hand2^tm1Cse; Osr2^tm2(cre)Jian/Osr2⁺
• Genetic Background: involves: 129S1/Sv * 129S7/SvEvBrd * C57BL/6

craniofacial

mandible hypoplasia ( J:149232 )

• mandible is hypoplastic

• cleft palate is not observed

skeleton

mandible hypoplasia ( J:149232 )

• mandible is hypoplastic

• cleft palate is not observed

Genotype
MGI:3715254

cn5

• Allelic Composition: Hand2^tm1Cse/Hand2^tm1Cse; H2az2^{Tg(Wnt1-cre)11Rth}/H2az2⁺
• Genetic Background: involves: 129S1/Sv * 129S7/SvEvBrd * C57BL/6 * CBA

craniofacial

craniofacial phenotype ( J:149232 )

N • palate is normal

N • no changes in cell proliferation or apoptosis are observed in palatal shelves at E13.5

Genotype
MGI:3848967

cn6

• Allelic Composition: Hand2^tm1Cse/Hand2^tm1Dsr; H2az2^{Tg(Wnt1-cre)11Rth}/H2az2⁺
• Genetic Background: involves: 129S1/Sv * 129S7/SvEvBrd * C57BL/6 * CBA

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:122604 )

• embryos begin to die by 12 dpc and no live embryos are recovered at 13 dpc

cardiovascular system

visceral vascular congestion ( J:122604 )

• blood pools in major vessels, heart, liver, and coelom by 12 dpc

abnormal blood circulation ( J:122604 )

• circulatory defects develop by 12 dpc

homeostasis/metabolism

abnormal enzyme/coenzyme level ( J:122604 )

• number of neuronal cells in sympathetic nervous system expressing tyrosine hydroxylase or dopamine beta-hydroxylase is greatly reduced compared to controls at 12.5 dpc

nervous system

nervous system phenotype ( J:122604 )

N • neural crest cell colonization of the sympathetic nervous system is normal, and sympathetic nervous system differentiation is unaffected in mutant embryos

abnormal adrenergic neuron morphology ( J:122604 )

• catecholaminergic differentiation of the sympathetic nervous system is abnormal in mutants; fewer neurons produce enzymes needed for synthesis of noradrenaline than in wild-type controls

Genotype
MGI:4417976

cn7

• Allelic Composition: Hand2^tm1Cse/Hand2⁺; H2az2^{Tg(Wnt1-cre)11Rth}/H2az2⁺
• Genetic Background: involves: 129S1/Sv * C57BL/6J * CBA/J

mortality/aging

lethality throughout fetal growth and development, complete penetrance ( J:155265 )

• no viable embryos are found at 15.5 dpc, with death prior to complete development of the cardiovascular system

• when pregnant mothers are treated with isoproterenol, approximately half of the mutant embryos survive to 15.5 dpc with about the same number surviving to birth

embryo

embryo phenotype ( J:155265 )

N • neural crest cell migration and smooth muscle differentiation are unaffected

cardiovascular system

pulmonary artery stenosis ( J:155265 )

• pulmonary stenosis is observed at 16.5 dpc (in 37.5% of mutants)

aberrant origin of the right subclavian artery ( J:155265 )

• embryos show abnormal origin of the right subclavian artery including retroesophageal right subclavian artery at 16.5 dpc (in 100% of mutants)

retroesophageal right subclavian artery ( J:155265 )

• observed at 16.5 dpc (in 87.5% of mutants)

interrupted aortic arch ( J:155265 )

• observed at 16.5 dpc (in 62.5% of mutants)

abnormal myocardial trabeculae morphology ( J:155265 )

• hypertrabeculation in the right ventricle is observed at 17.5 dpc due to decrease in number of cells exiting the cell cycle

heart right ventricle hypertrophy ( J:155265 )

• size of right ventricle is increased in embryos at 17.5 dpc

perimembraneous ventricular septal defect ( J:155265 )

• embyos display membranous ventricular defects at 16.5 dpc (in 100% of mutants)

abnormal fetal cardiomyocyte proliferation ( J:155265 )

• proliferation is increased 2-fold over controls in trabecular zone of the right ventricle at 13.5 and 15.5 dpc with no increase observed in the compact zone of the heart or the trabecular zone of the left ventricle

muscle

abnormal myocardial trabeculae morphology ( J:155265 )

• hypertrabeculation in the right ventricle is observed at 17.5 dpc due to decrease in number of cells exiting the cell cycle

heart right ventricle hypertrophy ( J:155265 )

• size of right ventricle is increased in embryos at 17.5 dpc

abnormal fetal cardiomyocyte proliferation ( J:155265 )

• proliferation is increased 2-fold over controls in trabecular zone of the right ventricle at 13.5 and 15.5 dpc with no increase observed in the compact zone of the heart or the trabecular zone of the left ventricle

cellular

abnormal fetal cardiomyocyte proliferation ( J:155265 )

• proliferation is increased 2-fold over controls in trabecular zone of the right ventricle at 13.5 and 15.5 dpc with no increase observed in the compact zone of the heart or the trabecular zone of the left ventricle

abnormal cell cycle ( J:155265 )

• doubling in proportion of cycling cardiomyocytes is detected in trabecular zone of right ventricle

hematopoietic system

abnormal thymus development ( J:155265 )

• the thymus is located lateral to the aortic arch arteries in a more rostral position compared to the normal location on the ventral side of the outflow tract close to the heart

immune system

abnormal thymus development ( J:155265 )

• the thymus is located lateral to the aortic arch arteries in a more rostral position compared to the normal location on the ventral side of the outflow tract close to the heart

endocrine/exocrine glands

abnormal thymus development ( J:155265 )

• the thymus is located lateral to the aortic arch arteries in a more rostral position compared to the normal location on the ventral side of the outflow tract close to the heart

growth/size/body

heart right ventricle hypertrophy ( J:155265 )

• size of right ventricle is increased in embryos at 17.5 dpc

Genotype
MGI:4417974

cn8

• Allelic Composition: Hand2^tm1Cse/Hand2⁺; Tg(Tnnt2-cre)5Blh/0
• Genetic Background: involves: 129S1/Sv * C57BL/6J * DBA/2

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:155265 )

• embryos survive at the expected Mendelian ratio until 9.5 dpc, with viablility dropping until 12.5 dpc after which no viable embryos are recovered

cardiovascular system

abnormal cardiac outflow tract development ( J:155265 )

• at 12.5 dpc, surviving embryos show hypoplastic outflow tract

abnormal heart ventricle morphology ( J:155265 )

• at 10.5 dpc severely affected embryos exhibit only a single clearly defined ventricle

decreased heart right ventricle size ( J:155265 )

• at 12.5 dpc, surviving embryos show hypoplastic right ventricle

Genotype
MGI:4417975

cn9

• Allelic Composition: Hand2^tm1Cse/Hand2⁺; Tg(Hoxb6-cre)#Mku/0
• Genetic Background: involves: 129S1/Sv * FVB/N

mortality/aging

mortality/aging ( J:155265 )

N • embryos are viable to birth

embryo

embryo phenotype ( J:155265 )

N • no visible defects are observed in extraembryonic mesoderm formation

limbs/digits/tail

abnormal limb development ( J:155265 )

• mutant neonates exhibit severe limb deformities

cardiovascular system

cardiovascular system phenotype ( J:155265 )

N • no visible defects are observed in blood vessel formation