Phenotypes associated with this allele

• Allele Symbol: Braf^tm1Bbd
• Allele Name: targeted mutation 1, Mariano Barbacid
• Allele ID: MGI:4946645
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
ht1	Braf^tm1Bbd/Braf^+	B6.129-Braf^tm1Bbd	MGI:4946650
ht2	Braf^tm1Bbd/Braf^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6J	MGI:4946646
ht3	Braf^tm1Bbd/Braf^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * CD-1	MGI:4946647

Genotype
MGI:4946650

ht1

• Allelic Composition: Braf^tm1Bbd/Braf⁺
• Genetic Background: B6.129-Braf^tm1Bbd

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

mortality/aging

premature death ( J:170095 )

• most mice die before 12 weeks of age

• Background Sensitivity: life span is reduced compared to mice on a mixed 129 and C57BL/6J background

craniofacial

abnormal basicranium morphology ( J:170095 )

• mild defects

abnormal neurocranium morphology ( J:170095 )

• defects in the shape of the skull vault

abnormal frontal bone morphology ( J:170095 )

abnormal parietal bone morphology ( J:170095 )

round head ( J:170095 )

• rounder and shorter head

shortened head ( J:170095 )

• rounder and shorter head

growth/size/body

enlarged heart ( J:170095 )

• increase in the heart to body weight ratio

round head ( J:170095 )

• rounder and shorter head

shortened head ( J:170095 )

• rounder and shorter head

decreased body size ( J:170095 )

• by P5

• phenotype becomes worse with age

decreased body weight ( J:170095 )

• by P5

• phenotype becomes worse with age

behavior/neurological

hyperactivity ( J:170095 )

• characterized by increase in the frequency of repetitive movements and locomotion

increased locomotor activity ( J:170095 )

abnormal mating frequency ( J:170095 )

• males fail to mate but are not infertile

• Background Sensitivity: crossing onto a CD1 background reduces the breeding problems

cardiovascular system

enlarged heart ( J:170095 )

• increase in the heart to body weight ratio

vision/eye

cataract ( J:170095 )

• seen in 40% of mice by 8 weeks of age

• incidence increases with age

immune system

abnormal thymus morphology ( J:170095 )

• thymic disorganization and atrophy is seen in mice that become ill by 3 weeks of age

thymus atrophy ( J:170095 )

• in mice that become ill by 3 weeks of age

decreased thymocyte number ( J:170095 )

• decrease in the number of immature terminal deoxynucleotidyl transferase (TdT)-positive thymocytes in mice that become ill by 3 weeks of age

abnormal immune system physiology ( J:170095 )

• all tissues with lymphoid aggregates show massive apoptosis in mice that become ill by 3 weeks of age

increased thymocyte apoptosis ( J:170095 )

• in mice that become ill by 3 weeks of age

increased splenocyte apoptosis ( J:170095 )

• massive apoptosis in the spleen white pulp in mice that become ill by 3 weeks of age

cellular

abnormal cell morphology ( J:170095 )

• most cells show a reduction in the cytoplasm to nucleus ratio in mice that become ill by 3 weeks of age

• this reduction is more evident in the kidney and in pancreatic acinar cells

increased thymocyte apoptosis ( J:170095 )

• in mice that become ill by 3 weeks of age

increased splenocyte apoptosis ( J:170095 )

• massive apoptosis in the spleen white pulp in mice that become ill by 3 weeks of age

endocrine/exocrine glands

increased thymocyte apoptosis ( J:170095 )

• in mice that become ill by 3 weeks of age

abnormal pancreatic acinar cell morphology ( J:170095 )

• cells show a reduction in the cytoplasm to nucleus ratio in mice that become ill by 3 weeks of age

abnormal thymus morphology ( J:170095 )

• thymic disorganization and atrophy is seen in mice that become ill by 3 weeks of age

thymus atrophy ( J:170095 )

• in mice that become ill by 3 weeks of age

decreased thymocyte number ( J:170095 )

• decrease in the number of immature terminal deoxynucleotidyl transferase (TdT)-positive thymocytes in mice that become ill by 3 weeks of age

abnormal skin sebaceous gland morphology ( J:170095 )

• about 50% of mice that become ill by 3 weeks of age have reduced numbers and size of sebaceous glands in the skin

integument

abnormal skin sebaceous gland morphology ( J:170095 )

• about 50% of mice that become ill by 3 weeks of age have reduced numbers and size of sebaceous glands in the skin

adipose tissue

decreased white adipose tissue amount ( J:170095 )

• in about 50% of mice that become ill by 3 weeks of age

digestive/alimentary system

abnormal pancreatic acinar cell morphology ( J:170095 )

• cells show a reduction in the cytoplasm to nucleus ratio in mice that become ill by 3 weeks of age

renal/urinary system

abnormal kidney morphology ( J:170095 )

• cells show a reduction in the cytoplasm to nucleus ratio in mice that become ill by 3 weeks of age

decreased creatinine clearance ( J:170095 )

• at 2 months of age

oliguria ( J:170095 )

• at 2 months of age

skeleton

abnormal basicranium morphology ( J:170095 )

• mild defects

abnormal neurocranium morphology ( J:170095 )

• defects in the shape of the skull vault

abnormal frontal bone morphology ( J:170095 )

abnormal parietal bone morphology ( J:170095 )

hematopoietic system

increased thymocyte apoptosis ( J:170095 )

• in mice that become ill by 3 weeks of age

increased splenocyte apoptosis ( J:170095 )

• massive apoptosis in the spleen white pulp in mice that become ill by 3 weeks of age

abnormal thymus morphology ( J:170095 )

• thymic disorganization and atrophy is seen in mice that become ill by 3 weeks of age

thymus atrophy ( J:170095 )

• in mice that become ill by 3 weeks of age

decreased thymocyte number ( J:170095 )

• decrease in the number of immature terminal deoxynucleotidyl transferase (TdT)-positive thymocytes in mice that become ill by 3 weeks of age

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
cardiofaciocutaneous syndrome		DOID:0060233	OMIM:PS115150	J:170095

Genotype
MGI:4946646

ht2

• Allelic Composition: Braf^tm1Bbd/Braf⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6J

mortality/aging

premature death ( J:170095 )

• very few mice survive beyond 30 weeks of life

• Background Sensitivity: life span is increased compared to mice on an inbred C57BL/6J background but decreased compared to mice on a mixed 129, C57BL/6J and CD-1 background

postnatal lethality, incomplete penetrance ( J:170095 )

• 35% of mice die during the first 3 weeks of life

craniofacial

abnormal basicranium morphology ( J:170095 )

• mild defects

abnormal neurocranium morphology ( J:170095 )

• defects in the shape of the skull vault

abnormal frontal bone morphology ( J:170095 )

abnormal parietal bone morphology ( J:170095 )

round head ( J:170095 )

• rounder and shorter head

shortened head ( J:170095 )

• rounder and shorter head

growth/size/body

enlarged heart ( J:170095 )

• increase in the heart to body weight ratio

round head ( J:170095 )

• rounder and shorter head

shortened head ( J:170095 )

• rounder and shorter head

decreased body size ( J:170095 )

• by P5

• phenotype becomes worse with age

decreased body weight ( J:170095 )

• by P5

• phenotype becomes worse with age

behavior/neurological

hyperactivity ( J:170095 )

• characterized by increase in the frequency of repetitive movements and locomotion

increased locomotor activity ( J:170095 )

abnormal mating frequency ( J:170095 )

• males fail to mate but are not infertile

• Background Sensitivity: crossing onto a CD1 background reduces the breeding problems

cardiovascular system

enlarged heart ( J:170095 )

• increase in the heart to body weight ratio

vision/eye

cataract ( J:170095 )

• seen in 40% of mice by 8 weeks of age

• incidence increases with age

immune system

abnormal thymus morphology ( J:170095 )

• thymic disorganization and atrophy is seen in mice that become ill by 3 weeks of age

thymus atrophy ( J:170095 )

• in mice that become ill by 3 weeks of age

decreased thymocyte number ( J:170095 )

• decrease in the number of immature terminal deoxynucleotidyl transferase (TdT)-positive thymocytes in mice that become ill by 3 weeks of age

abnormal immune system physiology ( J:170095 )

• all tissues with lymphoid aggregates show massive apoptosis in mice that become ill by 3 weeks of age

increased thymocyte apoptosis ( J:170095 )

• in mice that become ill by 3 weeks of age

increased splenocyte apoptosis ( J:170095 )

• massive apoptosis in the spleen white pulp in mice that become ill by 3 weeks of age

cellular

abnormal cell morphology ( J:170095 )

• most cells show a reduction in the cytoplasm to nucleus ratio in mice that become ill by 3 weeks of age

• this reduction is more evident in the kidney and in pancreatic acinar cells

increased thymocyte apoptosis ( J:170095 )

• in mice that become ill by 3 weeks of age

increased splenocyte apoptosis ( J:170095 )

• massive apoptosis in the spleen white pulp in mice that become ill by 3 weeks of age

endocrine/exocrine glands

increased thymocyte apoptosis ( J:170095 )

• in mice that become ill by 3 weeks of age

abnormal pancreatic acinar cell morphology ( J:170095 )

• cells show a reduction in the cytoplasm to nucleus ratio in mice that become ill by 3 weeks of age

abnormal thymus morphology ( J:170095 )

• thymic disorganization and atrophy is seen in mice that become ill by 3 weeks of age

thymus atrophy ( J:170095 )

• in mice that become ill by 3 weeks of age

decreased thymocyte number ( J:170095 )

• decrease in the number of immature terminal deoxynucleotidyl transferase (TdT)-positive thymocytes in mice that become ill by 3 weeks of age

abnormal skin sebaceous gland morphology ( J:170095 )

• about 50% of mice that become ill by 3 weeks of age have reduced numbers and size of sebaceous glands in the skin

integument

abnormal skin sebaceous gland morphology ( J:170095 )

• about 50% of mice that become ill by 3 weeks of age have reduced numbers and size of sebaceous glands in the skin

adipose tissue

decreased white adipose tissue amount ( J:170095 )

• in about 50% of mice that become ill by 3 weeks of age

homeostasis/metabolism

increased circulating noradrenaline level ( J:170095 )

• at 5 months of age

renal/urinary system

abnormal kidney morphology ( J:170095 )

• cells show a reduction in the cytoplasm to nucleus ratio in mice that become ill by 3 weeks of age

digestive/alimentary system

abnormal pancreatic acinar cell morphology ( J:170095 )

• cells show a reduction in the cytoplasm to nucleus ratio in mice that become ill by 3 weeks of age

skeleton

abnormal basicranium morphology ( J:170095 )

• mild defects

abnormal neurocranium morphology ( J:170095 )

• defects in the shape of the skull vault

abnormal frontal bone morphology ( J:170095 )

abnormal parietal bone morphology ( J:170095 )

hematopoietic system

increased thymocyte apoptosis ( J:170095 )

• in mice that become ill by 3 weeks of age

increased splenocyte apoptosis ( J:170095 )

• massive apoptosis in the spleen white pulp in mice that become ill by 3 weeks of age

abnormal thymus morphology ( J:170095 )

• thymic disorganization and atrophy is seen in mice that become ill by 3 weeks of age

thymus atrophy ( J:170095 )

• in mice that become ill by 3 weeks of age

decreased thymocyte number ( J:170095 )

• decrease in the number of immature terminal deoxynucleotidyl transferase (TdT)-positive thymocytes in mice that become ill by 3 weeks of age

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
cardiofaciocutaneous syndrome		DOID:0060233	OMIM:PS115150	J:170095

Genotype
MGI:4946647

ht3

• Allelic Composition: Braf^tm1Bbd/Braf⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * CD-1

mortality/aging

premature death ( J:170095 )

• about 60% of mice survive past 40 weeks of age

• Background Sensitivity: life span is increased compared to mice on an inbred C57BL/6J or a mixed 129 and C57BL/6J background

craniofacial

abnormal basicranium morphology ( J:170095 )

• mild defects

abnormal neurocranium morphology ( J:170095 )

• defects in the shape of the skull vault

abnormal frontal bone morphology ( J:170095 )

abnormal parietal bone morphology ( J:170095 )

round head ( J:170095 )

• rounder and shorter head

shortened head ( J:170095 )

• rounder and shorter head

growth/size/body

enlarged heart ( J:170095 )

• increase in the heart to body weight ratio

heart hyperplasia ( J:170095 )

round head ( J:170095 )

• rounder and shorter head

shortened head ( J:170095 )

• rounder and shorter head

decreased body size ( J:170095 )

• by P5

• phenotype becomes worse with age

decreased body weight ( J:170095 )

• by P5

• phenotype becomes worse with age

behavior/neurological

hyperactivity ( J:170095 )

• characterized by increase in the frequency of repetitive movements and locomotion

increased locomotor activity ( J:170095 )

abnormal mating frequency ( J:170095 )

• males fail to mate but are not infertile

• Background Sensitivity: crossing onto a CD1 background reduces the breeding problems

convulsive seizures ( J:170095 )

• develop epileptic seizures around 12 weeks of age

• incidence of mice with seizures increase with age until about 20 weeks of age

• seizures appear in response to handling

cardiovascular system

enlarged heart ( J:170095 )

• increase in the heart to body weight ratio

heart hyperplasia ( J:170095 )

increased cardiac muscle contractility ( J:170095 )

• increase in the ejection fraction and a decrease in the end diastolic and systolic volumes

• however, no difference in systolic arterial blood pressure is detected compared to wild-type controls

vision/eye

cataract ( J:170095 )

• seen in 40% of mice by 8 weeks of age

• incidence increases with age

neoplasm

increased gland tumor incidence ( J:170095 )

• develop paragangliomas at a high frequency (20 of 25 mice) and with a short latency (about 5 months)

increased pheochromocytoma incidence ( J:170095 )

• develop pheochromocytomas at a high frequency (20 of 25 mice) and with a short latency (about 5 months)

increased metastatic potential ( J:170095 )

• about 20% of tumor bearing mice show metastatis to distant tissue

increased lung adenoma incidence ( J:170095 )

• a few mice develop lung adenomas (grades II-III)

integument

abnormal skin sebaceous gland morphology ( J:170095 )

• about 50% of mice that become ill by 3 weeks of age have reduced numbers and size of sebaceous glands in the skin

abnormal dermal melanocyte morphology ( J:170095 )

• melanocytic hyperplasia in the dermis

cellular

abnormal cell morphology ( J:170095 )

• most cells show a reduction in the cytoplasm to nucleus ratio in mice that become ill by 3 weeks of age

• this reduction is more evident in the kidney and in pancreatic acinar cells

increased thymocyte apoptosis ( J:170095 )

• in mice that become ill by 3 weeks of age

increased splenocyte apoptosis ( J:170095 )

• massive apoptosis in the spleen white pulp in mice that become ill by 3 weeks of age

immune system

abnormal thymus morphology ( J:170095 )

• thymic disorganization and atrophy is seen in mice that become ill by 3 weeks of age

thymus atrophy ( J:170095 )

• in mice that become ill by 3 weeks of age

decreased thymocyte number ( J:170095 )

• decrease in the number of immature terminal deoxynucleotidyl transferase (TdT)-positive thymocytes in mice that become ill by 3 weeks of age

abnormal immune system physiology ( J:170095 )

• all tissues with lymphoid aggregates show massive apoptosis in mice that become ill by 3 weeks of age

increased thymocyte apoptosis ( J:170095 )

• in mice that become ill by 3 weeks of age

increased splenocyte apoptosis ( J:170095 )

• massive apoptosis in the spleen white pulp in mice that become ill by 3 weeks of age

adipose tissue

decreased white adipose tissue amount ( J:170095 )

• in about 50% of mice that become ill by 3 weeks of age

endocrine/exocrine glands

increased thymocyte apoptosis ( J:170095 )

• in mice that become ill by 3 weeks of age

abnormal pancreatic acinar cell morphology ( J:170095 )

• cells show a reduction in the cytoplasm to nucleus ratio in mice that become ill by 3 weeks of age

abnormal thymus morphology ( J:170095 )

• thymic disorganization and atrophy is seen in mice that become ill by 3 weeks of age

thymus atrophy ( J:170095 )

• in mice that become ill by 3 weeks of age

decreased thymocyte number ( J:170095 )

• decrease in the number of immature terminal deoxynucleotidyl transferase (TdT)-positive thymocytes in mice that become ill by 3 weeks of age

abnormal skin sebaceous gland morphology ( J:170095 )

• about 50% of mice that become ill by 3 weeks of age have reduced numbers and size of sebaceous glands in the skin

increased gland tumor incidence ( J:170095 )

• develop paragangliomas at a high frequency (20 of 25 mice) and with a short latency (about 5 months)

increased pheochromocytoma incidence ( J:170095 )

• develop pheochromocytomas at a high frequency (20 of 25 mice) and with a short latency (about 5 months)

renal/urinary system

abnormal kidney morphology ( J:170095 )

• cells show a reduction in the cytoplasm to nucleus ratio in mice that become ill by 3 weeks of age

respiratory system

increased lung adenoma incidence ( J:170095 )

• a few mice develop lung adenomas (grades II-III)

tachypnea ( J:170095 )

• at 4 months of age

nervous system

convulsive seizures ( J:170095 )

• develop epileptic seizures around 12 weeks of age

• incidence of mice with seizures increase with age until about 20 weeks of age

• seizures appear in response to handling

abnormal astrocyte morphology ( J:170095 )

• increase in the number of astrocytes in the brain at 8 weeks of age, independent of seizures

pigmentation

abnormal dermal melanocyte morphology ( J:170095 )

• melanocytic hyperplasia in the dermis

muscle

increased cardiac muscle contractility ( J:170095 )

• increase in the ejection fraction and a decrease in the end diastolic and systolic volumes

• however, no difference in systolic arterial blood pressure is detected compared to wild-type controls

skeleton

abnormal basicranium morphology ( J:170095 )

• mild defects

abnormal neurocranium morphology ( J:170095 )

• defects in the shape of the skull vault

abnormal frontal bone morphology ( J:170095 )

abnormal parietal bone morphology ( J:170095 )

digestive/alimentary system

abnormal pancreatic acinar cell morphology ( J:170095 )

• cells show a reduction in the cytoplasm to nucleus ratio in mice that become ill by 3 weeks of age

hematopoietic system

increased thymocyte apoptosis ( J:170095 )

• in mice that become ill by 3 weeks of age

increased splenocyte apoptosis ( J:170095 )

• massive apoptosis in the spleen white pulp in mice that become ill by 3 weeks of age

abnormal thymus morphology ( J:170095 )

• thymic disorganization and atrophy is seen in mice that become ill by 3 weeks of age

thymus atrophy ( J:170095 )

• in mice that become ill by 3 weeks of age

decreased thymocyte number ( J:170095 )

• decrease in the number of immature terminal deoxynucleotidyl transferase (TdT)-positive thymocytes in mice that become ill by 3 weeks of age

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
cardiofaciocutaneous syndrome		DOID:0060233	OMIM:PS115150	J:170095