Phenotypes associated with this allele

• Allele Symbol: Braf^tm1Zim
• Allele Name: targeted mutation 1, Andreas Zimmer
• Allele ID: MGI:1857579
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Braf^tm1Zim/Braf^tm1Zim	involves: 129	MGI:2662387
hm2	Braf^tm1Zim/Braf^tm1Zim	involves: 129/Sv * C57BL/6 * CD-1	MGI:3710366

Genotype
MGI:2662387

hm1

• Allelic Composition: Braf^tm1Zim/Braf^tm1Zim
• Genetic Background: involves: 129

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

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:41257 )

• homozygotes die between E10.5 and E12.5; no viable homozygotes are detected after E12.5

embryo

abnormal vitelline vasculature morphology ( J:41257 )

• homozygotes exhibit lack of circulation in the yolk sacs

decreased embryo weight ( J:41257 )

• at E10.5, homozygotes display a ~23% reduction in embryonic weight along with a ~30% reduction in total protein content

• however, this embryonic growth deficit does not appear to be the result of a developmental arrest

cardiovascular system

abnormal blood vessel morphology ( J:41257 )

• 66% of E10.5, 80% of E11.5, and 100% of E12.5 homozygotes display vascular defects

• at E12.5, all homozygotes display enlarged and abnormally shaped large blood vessels

abnormal aorta morphology ( J:41257 )

• at E12.5, homozygotes exhibit an abnormal and enlarged aorta

abnormal vascular endothelial cell morphology ( J:41257 )

• at E12.5, nearly all large blood vessels are insufficiently lined with endothelial cells

• multiple ruptures in the endothelial cell layer lead to extravasation of blood cells

increased vascular endothelial cell number ( J:41257 )

• after E10.5, homozygotes display an increased recruitment or proliferation of cells of the endothelial lineage

abnormal cardinal vein morphology ( J:41257 )

• at E11.5, mutant cardinal veins are enlarged and display multiple ruptures of the endothelial layer leading to extravasation of blood

abnormal vitelline vasculature morphology ( J:41257 )

• homozygotes exhibit lack of circulation in the yolk sacs

hematoma ( J:41257 )

• prior to E10.5, live homozygotes frequently exhibit hematomas in their pericardia

hemorrhage ( J:41257 )

• at E12.5, homozygotes display hemorrhage in the ventral region of the trunk

hemopericardium ( J:41257 )

• at E12.5, homozygotes display hemorrhage in the pericardial cavity and in all major body cavities

intraventricular hemorrhage ( J:41257 )

• at E12.5, homozygotes display hemorrhage into the brain ventricles

poor circulation ( J:41257 )

• reduced blood circulation in the embryo and yolk sac

decreased heart rate ( J:41257 )

• prior to E10.5, live homozygotes display a markedly slow heart beat

growth/size/body

decreased embryo weight ( J:41257 )

• however, this embryonic growth deficit does not appear to be the result of a developmental arrest

• at E10.5, homozygotes display a ~23% reduction in embryonic weight along with a ~30% reduction in total protein content

abnormal head morphology ( J:41257 )

• at E12.5, homozygotes display an abnormal head region

cellular

abnormal apoptosis ( J:41257 )

• at E11.5, some mutant embryos show a highly aberrant pattern of apoptosis in the neural tube and in mesodermal tissues; however, the number of apoptotic cells is not increased in these tissues relative to wild-type

• at E10.5, mutant but not wild-type embryos exhibit endothelial cell death in vasculogenesis-derived vessels (e.g. dorsal aorta and lingual artery), in angiogenesis-derived vessels (e.g. the perineural vascular plexus and the capillaries growing towards the lumen of the neural tube) and in the endocardium, as shown by TUNEL analysis

nervous system

intraventricular hemorrhage ( J:41257 )

• at E12.5, homozygotes display hemorrhage into the brain ventricles

abnormal neuron morphology ( J:41257 )

• mutant embryos display neuronal defects (not shown)

homeostasis/metabolism

hemopericardium ( J:41257 )

• at E12.5, homozygotes display hemorrhage in the pericardial cavity and in all major body cavities

Genotype
MGI:3710366

hm2

• Allelic Composition: Braf^tm1Zim/Braf^tm1Zim
• Genetic Background: involves: 129/Sv * C57BL/6 * CD-1

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:112971 )

• embryos do not survive past E12.5

nervous system

abnormal telencephalon development ( J:112971 )

• at E10.5, and more profoundly at E12.5, the cortical neurons (TBB1+) in the preplate layer are reduced twofold, disorganized and dispersed in the cortex

• at E10.5 and E12.5, the number of metaphase cells (pH3+) is increased and more ectopic cells are found

• at E10.5 and E12.5, many apoptotic cells (CASP3+) are found in the central part of the sagittal sections including some neurons (TBB1+) unlike controls in which no apoptosis is observed

• at E12.5, there is a 2-fold reduction in cortical neurons (TBB1+) and slight reduction in proliferation with proliferating cells confined to the basal half of the ventricular zone