Phenotypes associated with this allele

• Allele Symbol: Hira^tm1Pjs
• Allele Name: targeted mutation 1, Peter J Scambler
• Allele ID: MGI:2178130
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Hira^tm1Pjs/Hira^tm1Pjs	involves: 129S1/Sv * C57BL/6	MGI:3712812
hm2	Hira^tm1Pjs/Hira^tm1Pjs	involves: 129S1/Sv * C57BL/6 * CD-1	MGI:3712804

Genotype
MGI:3712812

hm1

• Allelic Composition: Hira^tm1Pjs/Hira^tm1Pjs
• Genetic Background: involves: 129S1/Sv * C57BL/6

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

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:75491 )

• Background Sensitivity: homozygotes die by E9.5, about a day earlier than on a mixed CD-1 background

growth/size/body

embryonic growth retardation ( J:75491 )

• development is severely delayed at early gastrulation in the worst affected embryos

• at E9.5, all embryos show a developmental delay of up to 24 hours

• Background Sensitivity: developmental delay and growth retardation are more prominent on the 129S1/Sv and C57BL/6 background than on the mixed CD-1 background

decreased embryo size ( J:75491 )

• smaller at E9.5

abnormal head morphology ( J:75491 )

• the least affected embryos have recognizable but abnormal head structures

abnormal head mesenchyme morphology ( J:75491 )

• mesenchyme is often deficient within the head

embryo

abnormal developmental patterning ( J:75491 )

abnormal embryo turning ( J:75491 )

• few E9.5 embryos have undergone embryo turning

abnormal mesendoderm development ( J:75491 )

• mesendodermal molecular markers show abnormal expression

failure to gastrulate ( J:75491 )

• Background Sensitivity: 53% of embryos are small balls of disorganized tissue at E9.5 on the mixed 129S1/Sv and C57BL/6 background, while only 7% are disorganized on the mixed CD-1 background

abnormal left-right axis patterning ( J:75491 )

• embryos often exhibit left-right asymmetry defects

embryonic growth arrest ( J:75491 )

• development is severely delayed or arrested at early gastrulation in the worst affected embryos

embryonic growth retardation ( J:75491 )

• development is severely delayed at early gastrulation in the worst affected embryos

• at E9.5, all embryos show a developmental delay of up to 24 hours

• Background Sensitivity: developmental delay and growth retardation are more prominent on the 129S1/Sv and C57BL/6 background than on the mixed CD-1 background

decreased embryo size ( J:75491 )

• smaller at E9.5

abnormal embryonic tissue morphology ( J:75491 )

abnormal pharyngeal arch morphology ( J:75491 )

• the least affected embryos have recognizable but abnormal branchial arches

abnormal axial mesoderm morphology ( J:75491 )

• abnormal axial mesoderm formation

• some axial mesoderm is formed in both mild and severely affected embryos, but normal axial structures are never present

abnormal head mesenchyme morphology ( J:75491 )

• mesenchyme is often deficient within the head

abnormal neural plate morphology ( J:75491 )

• the neural plate is often extended laterally with abnormal folding beyond its normal boundaries, especially in more caudal regions

abnormal neural tube morphology ( J:75491 )

• the neural tube is often missing

abnormal embryonic neuroepithelium morphology ( J:75491 )

• neural markers indicate that the neuroepithelium is disorganized and abnormally patterned

open neural tube ( J:75491 )

• when present, the neural tube is either severely kinked or open

kinked neural tube ( J:75491 )

• when present, the neural tube is either severely kinked or open

abnormal notochord morphology ( J:75491 )

• Background Sensitivity: in mildly affected embryos, the notochord is often absent or only detected at the mid- or hindbrain level on the 129S1/Sv and C57BL/6 background, however no notochord abnormalities are seen on the mixed CD-1 background

• ventral duplication of the notochord is seen in a few embryos

abnormal prechordal plate morphology ( J:75491 )

• in mildly affected embryos, the prechordal plate is often absent or only detected at the mid- or hindbrain level

abnormal primitive streak morphology ( J:75491 )

• primitive streak is distorted and contains increased numbers of cells in some embryos, resulting in the bulging out into the amniotic cavity

abnormal somite shape ( J:75491 )

• any somites that are found are asymmetric and do not have clear boundaries

decreased somite size ( J:75491 )

• any somites that are found are small

incomplete somite formation ( J:75491 )

• caudal to the level of the hindbrain-spinal cord boundary, the somites are rarely present

• in all embryos, no segmentation of the somatic mesoderm is observed at E9.5

embryonic-extraembryonic boundary constriction ( J:75491 )

• a subset of embryos have a constriction at the embryonic-extraembryonic junction

enlarged allantois ( J:75491 )

• Background Sensitivity: 67% of embryos exhibit allantois defects compared to 45% on the mixed CD-1 background

• 67% of embryos have a large allantois

failure of chorioallantoic fusion ( J:75491 )

• allantois does not fuse with the chorion in 67% of embryos; the unfused allantois remains either as a vesicle, which is sometimes blood-filled, or a solid structure of various shape

cardiovascular system

abnormal heart morphology ( J:75491 )

• the least affected embryos have recognizable but abnormal hearts

abnormal heart development ( J:75491 )

• embryos often show altered development of heart chambers

craniofacial

abnormal pharyngeal arch morphology ( J:75491 )

• the least affected embryos have recognizable but abnormal branchial arches

nervous system

abnormal neural plate morphology ( J:75491 )

• the neural plate is often extended laterally with abnormal folding beyond its normal boundaries, especially in more caudal regions

abnormal neural tube morphology ( J:75491 )

• the neural tube is often missing

abnormal embryonic neuroepithelium morphology ( J:75491 )

• neural markers indicate that the neuroepithelium is disorganized and abnormally patterned

open neural tube ( J:75491 )

• when present, the neural tube is either severely kinked or open

kinked neural tube ( J:75491 )

• when present, the neural tube is either severely kinked or open

abnormal brain development ( J:75491 )

• the brain often fails to fuse, resulting in an everted cap-like structure

abnormal hindbrain development ( J:75491 )

• marker analysis indicates abnormal hindbrain development

abnormal midbrain-hindbrain boundary development ( J:75491 )

• marker analysis indicates the disruption of the development of the midbrain-hindbrain border

Genotype
MGI:3712804

hm2

• Allelic Composition: Hira^tm1Pjs/Hira^tm1Pjs
• Genetic Background: involves: 129S1/Sv * C57BL/6 * CD-1

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:75491 )

• Background Sensitivity: homozygotes on a mixed CD-1 background die by E11, about a day later than on the 129S1/Sv and C57BL/6 background

growth/size/body

embryonic growth retardation ( J:75491 )

• Background Sensitivity: developmental delay and retarded growth are evident, but less apparent than on the 129S1/Sv and C57BL/6 background

abnormal head morphology ( J:75491 )

• the most severely affected embryos have recognizable but badly patterned head structures

embryo

embryo phenotype ( J:75491 )

N • Background Sensitivity: expression of notochord markers is normal, indicating normal axial mesoderm development, unlike on the 129S1/Sv and C57BL/6 background, in which notochord abnormalities are observed

abnormal vitelline vasculature morphology ( J:75491 )

• vascularization in the yolk sac is abnormal, with decreased number of large vessels branching off the main trunks and disorganized interlocking network of small blood vessels

abnormal embryo development ( J:75491 )

• 33% of embryos have a severe phenotype, while 60% have a much milder phenotype than observed on the 129S1/Sv and C57BL/6 background; mild phenotype embryos have turned and have relatively normal caudal structures, with notochord, neural tube, and somites present

abnormal embryo turning ( J:75491 )

• Background Sensitivity: the most severely affected embryos do not undergo turning and resemble the milder phenotype observed in the 129S1/Sv and C57BL/6 background

failure to gastrulate ( J:75491 )

• Background Sensitivity: only 7% of embryos on the CD-1 background are disorganized balls of tissue compared to 53% on 129S1/Sv and C57BL/6 background

abnormal rostral-caudal axis patterning ( J:75491 )

• the most severely affected embryos have abnormal or absent caudal axial structures

caudal body truncation ( J:75491 )

• absence of caudal axial structures

embryonic growth retardation ( J:75491 )

• Background Sensitivity: developmental delay and retarded growth are evident, but less apparent than on the 129S1/Sv and C57BL/6 background

abnormal paraxial mesoderm morphology ( J:75491 )

• in severely affected embryos, no segmentation of the somitic mesoderm is observed at E9.5

abnormal somite shape ( J:75491 )

• in some cases, somites are small, malformed, or asymmetric

decreased somite size ( J:75491 )

• in some cases, somites are small

abnormal allantois morphology ( J:75491 )

• Background Sensitivity: 45% of embryos exhibit allantois defects compared to 67% on the 129S1/Sv and C57BL/6 background

cardiovascular system

abnormal blood vessel morphology ( J:75491 )

• even in mildly affected embryos, very few large blood vessels connect the embryo to the placenta or to the yolk sac

• complex vascularization of the embryo is disrupted, with fewer vessels and larger patches of staining rather than a fine network

abnormal vitelline vasculature morphology ( J:75491 )

• vascularization in the yolk sac is abnormal, with decreased number of large vessels branching off the main trunks and disorganized interlocking network of small blood vessels

abnormal heart development ( J:75491 )

• in some embryos with normal looping, chamber formation is disrupted

failure of heart looping ( J:75491 )

• in 6 of 52 embryos, looping does not occur

abnormal heart tube morphology ( J:75491 )

• the heart chambers appear to balloon out of the linear heart tube, resulting in a dumbbell-shaped appearance, in some embryos

pericardial edema ( J:75491 )

• some embryos exhibit severe pericardial edema, more often in embryos with a linear heart tube

irregular heartbeat ( J:75491 )

• in some embryos, the heart beat is irregular, with blood being shuttled back and forth between the two chambers

homeostasis/metabolism

pericardial edema ( J:75491 )

• some embryos exhibit severe pericardial edema, more often in embryos with a linear heart tube

nervous system

abnormal brain development ( J:75491 )

• homozygotes display head defects, particularly the failure of the brain to fuse, resulting in the neuroepithelium of the brain to form large open everted cap-like structures

abnormal forebrain morphology ( J:75491 )

• distinct forebrain structures are not discerned in some embryos