Analysis Tools|
Allele Symbol Allele Name Allele ID |
Hand2tm1Dsr targeted mutation 1, Deepak Srivastava MGI:1857639 |
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| Summary |
14 genotypes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• at E9.0, mice exhibit increased apoptosis in the pharyngeal mesoderm and outflow tract compared with wild-type mice
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• severe
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• homozygous mutant embryos are present at the expected Mendelian ratios between E8.0-E10.0; however, no viable mutant embryos are detected shortly after E10.5 as a result of severe heart failure
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• by E10.0, homozygotes exhibit a small first branchial (aortic) arch artery
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• by E10.0, homozygotes exhibit no evidence of a second branchial arch artery
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• at E9.5, mutant embryos show significant dilation of the aortic sac
• by E10.5, the mutant aortic sac resembles a markedly dilated balloon-like structure
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• mutants exhibit an abrupt and aberrant connection between the cardiac outflow tract (conotruncus) and a single left-sided ventricular chamber
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• homozygotes initiate looping in the correct direction; however, looping advances to the stage where the atrium occupies a dorsal position relative to the ventricle
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• homozygotes exhibit an abrupt and aberrant connection between the cardiac outflow tract (conotruncus) and a single left-sided ventricular chamber
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• at E10.0, homozygotes fail to exhibit ventricular trabeculae, resulting in reduced contractility
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• homozygotes lack a distinguishable right-sided ventricular chamber of the heart
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• at E9.5, homozygotes show evidence of a marked pericardial effusion in the pericardial sac
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• by E10.0, homozygotes exhibit a small first branchial (aortic) arch artery
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• by E10.0, homozygotes exhibit no evidence of a second branchial arch artery
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• although of normal size at E9.5, mutant embryos exhibit growth retardation at E10.5
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• at E10.0, mutant forelimb buds appear variably dysmorphic, often exhibiting an anterior margin at the level of somite 8 or 9, instead of somite 7 as in wild-type embryos
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• at E10.0, mutant forelimb buds are extremely small
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• homozygotes form ~24 somites, with somites becoming progressively smaller towards the posterior end of the embryo, suggesting impaired trunk development
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• although of normal size at E9.5, mutant embryos exhibit growth retardation at E10.5
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• at E10.0, homozygotes fail to exhibit ventricular trabeculae, resulting in reduced contractility
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• at E9.5, homozygotes show evidence of a marked pericardial effusion in the pericardial sac
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• by E9.75, homozygotes exhibit severe edema, probably as a result of circulatory dysfunction
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• at E10.0, mutant forelimb buds appear variably dysmorphic, often exhibiting an anterior margin at the level of somite 8 or 9, instead of somite 7 as in wild-type embryos
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• at E10.0, mutant forelimb buds are extremely small
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• by E10.0, homozygotes exhibit a small first branchial (aortic) arch artery
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• by E10.0, homozygotes exhibit no evidence of a second branchial arch artery
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• homozygotes die of cardiac failure at ~E11
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• at E9.5, homozygotes fail to form a third and fourth branchial arch
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• at E9.5, homozygotes exhibit hypoplastic first and second branchial arches secondary to programmed cell death of the mesenchyme; only raised outlines of the third and fourth branchial arches are detectable at this stage
• by E10.0, mutants display acellularity in the ectomesenchyme of the first branchial arch and a severely hypoplastic second branchial arch
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• homozygotes become growth-retarded after E9.5
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• homozygotes develop only ~20-24 somites before dying of cardiac failure at ~E11
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• homozygotes become growth-retarded after E9.5
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• at E9.5, homozygotes exhibit extensive apoptosis in the mesenchyme of the first and second branchial arches, in the absence of a proliferative defect
• by E10.0, most mesenchymal cells have died, and loss of cellularity in the core of branchial arches is observed
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• at E9.5, homozygotes fail to form a third and fourth branchial arch
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• at E9.5, homozygotes exhibit hypoplastic first and second branchial arches secondary to programmed cell death of the mesenchyme; only raised outlines of the third and fourth branchial arches are detectable at this stage
• by E10.0, mutants display acellularity in the ectomesenchyme of the first branchial arch and a severely hypoplastic second branchial arch
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• pups die within a day of birth with cleft palates
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• newborn pups cannot feed
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• the primary palate forms, but growth is incomplete and primary palates fails to fuse with secondary palate
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• 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
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• at E13.5, shelves are positioned normally, but appear slightly smaller than controls
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• the secondary palate contains a wide cleft in the anterior and mid-section
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• 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
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• tongue is hypoplastic at E14.5
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• the primary palate forms, but growth is incomplete and primary palates fails to fuse with secondary palate
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• 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
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• at E13.5, shelves are positioned normally, but appear slightly smaller than controls
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• the secondary palate contains a wide cleft in the anterior and mid-section
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• 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
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• tongue is hypoplastic at E14.5
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• the primary palate forms, but growth is incomplete and primary palates fails to fuse with secondary palate
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• 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
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• at E13.5, shelves are positioned normally, but appear slightly smaller than controls
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• the secondary palate contains a wide cleft in the anterior and mid-section
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• 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
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• tongue is hypoplastic at E14.5
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• at E12.5, mice exhibit narrowed outflow tract and hypoplastic outlet or subpulmonary conus compared with wild-type mice
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• at E14.5, the right ventricular cavity is smaller than in wild-type mice
• however, the right ventricular muscle wall thickness is normal
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice die at E10.5
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• shortened
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• severe
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• at E9.0, mice exhibit increased apoptosis in the pharyngeal mesoderm compared with wild-type mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice die at E15.5
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• shortened at E10.5 and E13.5
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• at E13.5, but not at E10.5
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice die at E12.5
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• slightly at E9.5
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• slightly at E9.5
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice die at E13.5
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• immature truncus arteriosis
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• mice lack the anlage of the tricuspid valve between the right atrium and ventricle unlike wild-type mice
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• at E9.5 but not as severely as in Hand2tm1Dsr homozygotes
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• at E12.5
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• embryos begin to die by 12 dpc and no live embryos are recovered at 13 dpc
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• blood pools in major vessels, heart, liver, and coelom by 12 dpc
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• circulatory defects develop by 12 dpc
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• 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
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| N |
• neural crest cell colonization of the sympathetic nervous system is normal, and sympathetic nervous system differentiation is unaffected in mutant embryos
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• 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
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• at E9.5, mice exhibit fewer progenitor cells migration into the outflow tract compared with control mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• double homozygotes die between E9.5 and E10.5, i.e. one-half to one day earlier than homozygotes with either single gene disruption
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• by E9.5, double homozygotes display disruption of the extraembryonic and embryonic vasculature
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• double homozygotes display no trabeculae and little cardiac jelly in their single dorsal cardiac chamber
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• double homozygotes exhibit a thin outflow tract
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• in double homozygotes, the posterior part of the single dorsally located cardiac chamber is connected to bilaterally dilated sinus venosae, indicating hemodynamic insufficiency
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• at E9.25, double homozygotes display only a single dorsally located cardiac chamber, which is slightly oriented to the left and is molecularly identified as an atrium
• no evidence of a ventral chamber is observed
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• double homozygotes display complete ventricular dysgenesis
• a small pool of cardiomyocytes expressing ventricular-specific markers is observed along the ventral surface of the single atrial chamber, but fails to expand in number and form the ventricular chambers
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• by E9.5, double homozygotes begin to exhibit pericardial effusion, indicating heart failure despite continued rhythmical beating
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• double homozygotes display no trabeculae and little cardiac jelly in their single dorsal cardiac chamber
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• by E9.5, double homozygotes begin to exhibit pericardial effusion, indicating heart failure despite continued rhythmical beating
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• cardiac morphogenesis is comparable to both single mutants
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• myocardium shows a thin ventricular wall
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• exhibit poor caudal development compared to either single mutant
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• double heterozygotes are viable, fertile, and grow normally exhibiting a normal lifespan
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Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO) |
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last database update 11/19/2024 MGI 6.24 |
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