Phenotypes associated with this allele

• Allele Symbol: Hras^tm2Xbr
• Allele Name: targeted mutation 2, Xose R Bustelo
• Allele ID: MGI:3803587
• Summary: 1 genotype

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Hras^tm2Xbr/Hras^tm2Xbr	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * FVB/N	MGI:3805200

Genotype
MGI:3805200

hm1

• Allelic Composition: Hras^tm2Xbr/Hras^tm2Xbr
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * FVB/N

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

Virgin Hras^tm2Xbr/Hras^tm2Xbr females display mammary gland hyperplasia

muscle

heart left ventricle hypertrophy ( J:137729 )

• increased cardiomyocyte size

• elevated interstitial collagen deposition

heart right ventricle hypertrophy ( J:137729 )

• overall increase in size of walls and chamber

• cell size and density normal

neoplasm

neoplasm ( J:137729 )

N • most (19/20) mice are tumor free at 18 months of age whereas about 10% pf humans with a comparable mutation develop various tumors

increased mammary adenocarcinoma incidence ( J:137729 )

• one mouse in 20 has a mammary adenocarcinoma at 18 months

• epithelial in origin

endocrine/exocrine glands

abnormal mammary gland development ( J:137729 )

♀ • increased alveolar proliferation

♀ • slight decrease in adipose tissue

♀ • ductal ectasia

♀ • mild periductal-alveolar fibrosis

abnormal branching of the mammary ductal tree ( J:137729 )

♀ • increased ductal branching

♀ • greater ductal-lobulillar development

increased mammary adenocarcinoma incidence ( J:137729 )

• one mouse in 20 has a mammary adenocarcinoma at 18 months

• epithelial in origin

mammary gland hyperplasia ( J:137729 )

♀ • in females at around 4 months of age

craniofacial

abnormal cranium morphology ( J:137729 )

abnormal frontal bone morphology ( J:137729 )

• depression of anterior frontal bones

short premaxilla ( J:137729 )

short maxilla ( J:137729 )

• shortened maxilla

• shortened molar process

short zygomatic bone ( J:137729 )

abnormal facial morphology ( J:137729 )

• facial dysmorphia

• defects observed neonatally

abnormal lip morphology ( J:137729 )

• engrossed lips due to accumulation of adipocytes between skeletal muscle fascicules

• more sebaceous glands

• shorter elastin fibers

choanal stenosis ( J:137729 )

• narrowed choanae

depressed nasal bridge ( J:137729 )

• shortened and depressed nasal bridge

short nasal bridge ( J:137729 )

• shortened and depressed nasal bridge

cardiovascular system

cardiovascular system phenotype ( J:137729 )

N • heart rate normal

abnormal blood vessel morphology ( J:137729 )

• blood vessels generally more reactive to angiotensin II

abnormal aorta tunica media morphology ( J:137729 )

• develop severe thickening and remodeling of aorta media over time

abnormal heart morphology ( J:137729 )

• changes less pronounced at 6 months than at 4 months

• sarcomere organization normal

increased heart atrium size ( J:137729 )

• enlarged heart chambers at 4 months

• overall increase in size of walls and chambers

• cell size and density normal

enlarged aortic valve ( J:137729 )

• enlarged

• other heart valves normal

increased heart ventricle size ( J:137729 )

• enlarged heart chambers at 4 months

heart left ventricle hypertrophy ( J:137729 )

• increased cardiomyocyte size

• elevated interstitial collagen deposition

heart right ventricle hypertrophy ( J:137729 )

• overall increase in size of walls and chamber

• cell size and density normal

increased systemic arterial blood pressure ( J:137729 )

hypertension ( J:137729 )

• systemic hypertension

• at least partially due to elevated circulating levels of angiotensin II

• pulmonary blood pressure is normal

increased systemic arterial diastolic blood pressure ( J:137729 )

• anesthetized and conscious

increased systemic arterial systolic blood pressure ( J:137729 )

• anesthetized and conscious

renal/urinary system

renal/urinary system phenotype ( J:137729 )

N • urine production normal

N • sodium, potassium, chlorine excretion all normal

decreased urine creatinine level ( J:137729 )

renal fibrosis ( J:137729 )

homeostasis/metabolism

decreased urine creatinine level ( J:137729 )

increased circulating angiotensin II level ( J:137729 )

• elevated circulating levels of angiotensin II

respiratory system

respiratory system phenotype ( J:137729 )

N • breathing normal

choanal stenosis ( J:137729 )

• narrowed choanae

depressed nasal bridge ( J:137729 )

• shortened and depressed nasal bridge

short nasal bridge ( J:137729 )

• shortened and depressed nasal bridge

skeleton

abnormal cranium morphology ( J:137729 )

abnormal frontal bone morphology ( J:137729 )

• depression of anterior frontal bones

short premaxilla ( J:137729 )

short maxilla ( J:137729 )

• shortened maxilla

• shortened molar process

short zygomatic bone ( J:137729 )

integument

abnormal mammary gland development ( J:137729 )

♀ • increased alveolar proliferation

♀ • slight decrease in adipose tissue

♀ • ductal ectasia

♀ • mild periductal-alveolar fibrosis

abnormal branching of the mammary ductal tree ( J:137729 )

♀ • increased ductal branching

♀ • greater ductal-lobulillar development

increased mammary adenocarcinoma incidence ( J:137729 )

• one mouse in 20 has a mammary adenocarcinoma at 18 months

• epithelial in origin

mammary gland hyperplasia ( J:137729 )

♀ • in females at around 4 months of age

abnormal vibrissa follicle morphology ( J:137729 )

• distention and rounding of vibrissal follicles

growth/size/body

heart left ventricle hypertrophy ( J:137729 )

• increased cardiomyocyte size

• elevated interstitial collagen deposition

heart right ventricle hypertrophy ( J:137729 )

• overall increase in size of walls and chamber

• cell size and density normal

abnormal facial morphology ( J:137729 )

• facial dysmorphia

• defects observed neonatally

abnormal lip morphology ( J:137729 )

• engrossed lips due to accumulation of adipocytes between skeletal muscle fascicules

• more sebaceous glands

• shorter elastin fibers

choanal stenosis ( J:137729 )

• narrowed choanae

depressed nasal bridge ( J:137729 )

• shortened and depressed nasal bridge

short nasal bridge ( J:137729 )

• shortened and depressed nasal bridge

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Costello syndrome		DOID:0050469	OMIM:218040	J:137729