Phenotypes associated with this allele

• Allele Symbol: Chd2^{Gt(RRBO46)Byg}
• Allele Name: gene trap RRB046, BayGenomics
• Allele ID: MGI:3800602
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Chd2^Gt(RRBO46)Byg/Chd2^Gt(RRBO46)Byg	involves: 129P2/OlaHsd * C57BL/6	MGI:3838398
hm2	Chd2^Gt(RRBO46)Byg/Chd2^Gt(RRBO46)Byg	involves: 129P2/OlaHsd * C57BL/6J	MGI:5578001
ht3	Chd2^Gt(RRBO46)Byg/Chd2^+	involves: 129P2/OlaHsd * C57BL/6	MGI:3838399
ht4	Chd2^Gt(RRBO46)Byg/Chd2^+	involves: 129P2/OlaHsd * C57BL/6J	MGI:5515353

Genotype
MGI:3838398

hm1

• Allelic Composition: Chd2^{Gt(RRBO46)Byg}/Chd2^{Gt(RRBO46)Byg}
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

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

mortality/aging

postnatal lethality ( J:146176 )

postnatal lethality, complete penetrance ( J:146743 )

• while mice are present in Mendelian ratios at E18.5, no mice are observed at weaning

cellular

abnormal cell cycle ( J:146176 )

• X-ray exposed mouse embryonic fibroblasts exhibit a moderately higher increase in G1-S phase compared to similarly treated wild-type cells

increased cellular sensitivity to methylmethanesulfonate ( J:146176 )

increased cellular sensitivity to X-ray irradiation ( J:146176 )

increased cellular sensitivity to ultraviolet irradiation ( J:146176 )

abnormal DNA repair ( J:146176 )

• 25% of mouse embryonic fibroblasts (MEFs) exhibit numerous DNA breaks unlike wild-type MEFs

• treatment of MEFs with X-ray causes more DNA damage than in similarly treated wild-type MEFs that persists for longer than in wild-type MEFs

hematopoietic system

abnormal blood cell morphology/development ( J:146176 )

• clusters of hematopoietic cells are less organized compared to in wild-type mice

abnormal erythropoiesis ( J:146176 )

• mice exhibit impaired erythropoiesis with decreased expression of CD71 and CD117 but not Ter119 in fetal liver cells compared to in wild-type mice

increased megakaryocyte cell number ( J:146176 )

• in neonate livers

decreased erythroid progenitor cell number ( J:146176 )

• in neonate livers

cardiovascular system

abnormal blood vessel morphology ( J:146176 )

• at E12.5

hemorrhage ( J:146176 )

• at E12.5

behavior/neurological

lethargy ( J:146176 )

• loss of vitality

growth/size/body

decreased fetal size ( J:146743 )

• at E18.5 but not E16.5

fetal growth retardation ( J:146743 )

• at E18.5, mice exhibit profound growth retardation compared to wild-type mice

homeostasis/metabolism

abnormal DNA repair ( J:146176 )

• 25% of mouse embryonic fibroblasts (MEFs) exhibit numerous DNA breaks unlike wild-type MEFs

• treatment of MEFs with X-ray causes more DNA damage than in similarly treated wild-type MEFs that persists for longer than in wild-type MEFs

Genotype
MGI:5578001

hm2

• Allelic Composition: Chd2^{Gt(RRBO46)Byg}/Chd2^{Gt(RRBO46)Byg}
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6J

mortality/aging

postnatal lethality, complete penetrance ( J:137079 )

• despite some mice present at P1, no mice are present at weaning

lethality throughout fetal growth and development, incomplete penetrance ( J:137079 )

• fewer than expected mice are present at E14.5

cardiovascular system

increased heart atrium size ( J:137079 )

• mild to moderate in some neonates

growth/size/body

decreased body size ( J:137079 )

• neonates are runted

integument

pallor ( J:137079 )

• neonates are pale

vision/eye

abnormal eye morphology ( J:137079 )

• 2 of 15 mice exhibit defective eye formation and eye migration defects

anophthalmia ( J:137079 )

• in some mice

Genotype
MGI:3838399

ht3

• Allelic Composition: Chd2^{Gt(RRBO46)Byg}/Chd2⁺
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

mortality/aging

decreased survivor rate ( J:146176 , J:146743 )

• not all mice survive beyond weaning (J:146176)

• fewer than expected mice survive beyond weaning (J:146743)

premature death ( J:146176 , J:146743 )

• median lifespan of 52.3 weeks, most mice succumb to lymphomas by week 58, and all mice are dead by 100 weeks (J:146176)

• by 32 weeks of age 50% of mice die whereas all wild-type mice are alive (J:146743)

• by 64 weeks 94% of mice die whereas all wild-type mice are alive (J:146743)

postnatal lethality, incomplete penetrance ( J:146176 , J:146743 )

• some mice do not survive beyond weaning (J:146176)

• fewer than expected mice survive the first 4 days after birth (J:146743)

cardiovascular system

abnormal blood vessel morphology ( J:146176 )

• at E12.5

myocardial fiber degeneration ( J:146743 )

• primarily involving the left ventricular free wall and septum

enlarged heart ( J:146743 )

cardiac fibrosis ( J:146743 )

• primarily involving the left ventricular free wall and septum

hemorrhage ( J:146176 )

• at E12.5

pulmonary alveolar hemorrhage ( J:146743 )

arteritis ( J:146176 )

• artery inflammation

cardiomyopathy ( J:146743 )

heart inflammation ( J:146176 )

myocarditis ( J:146743 )

• in 57% of mice primarily involving the left ventricular free wall and septum

respiratory system

abnormal lung morphology ( J:146743 )

• discolored

pulmonary alveolar edema ( J:146743 )

abnormal respiratory system physiology ( J:146743 )

• 20% of mice exhibit lung alterations including interstitial pneumonia, alveolar hemorrhage, and alveolar edema

pulmonary alveolar hemorrhage ( J:146743 )

interstitial pneumonia ( J:146743 )

tachypnea ( J:146743 )

• as early as 16 weeks of age

liver/biliary system

bile duct hyperplasia ( J:146743 )

• minimal to mild

liver inflammation ( J:146743 )

• subacute

abnormal liver morphology ( J:146743 )

• nodular and discolored

hepatic necrosis ( J:146743 )

• centrilobular and coagulative in 28% of mice

renal/urinary system

abnormal kidney morphology ( J:146176 )

• mice exhibit nephropathy unlike wild-type mice

cortical renal glomerulopathies ( J:146743 )

• 85% of mice exhibit bilateral glomerulopathy with global glomerular enlargement due to hypercellularity and increased matrix amount unlike in wild-type mice

pale kidney ( J:146743 )

homeostasis/metabolism

pulmonary alveolar edema ( J:146743 )

lipidosis ( J:146743 )

• minimal to mild

hematopoietic system

increased T cell derived lymphoma incidence ( J:146176 )

extramedullary hematopoiesis ( J:146176 , J:146743 )

• in 67% of spleens due to an expansion of red pulp (J:146743)

increased CD4-positive, alpha-beta T cell number ( J:146176 )

• CD44 high CD4+ T cells are increased in mice with hyperplasia or lymphomas

decreased lymphocyte cell number ( J:146176 )

• in spleens and lymph nodes

abnormal spleen morphology ( J:146743 )

• dark spleens

enlarged spleen ( J:146743 )

increased spleen red pulp amount ( J:146743 )

• due to increased erythroid and myeloid cells

behavior/neurological

lethargy ( J:146743 )

• as early as 16 weeks of age

growth/size/body

enlarged heart ( J:146743 )

decreased birth body size ( J:146176 )

• reduction in body size compared to wild-type mice at birth

decreased body size ( J:146176 )

• the reduction in body size compared to wild-type mice observed at birth is less pronounced at 3 to 4 months of age

decreased body weight ( J:146743 )

• at P21

weight loss ( J:146176 )

• at 8 to 10 months of age

postnatal growth retardation ( J:146743 )

enlarged spleen ( J:146743 )

adipose tissue

decreased white adipose tissue amount ( J:146743 )

immune system

arteritis ( J:146176 )

• artery inflammation

heart inflammation ( J:146176 )

myocarditis ( J:146743 )

• in 57% of mice primarily involving the left ventricular free wall and septum

increased T cell derived lymphoma incidence ( J:146176 )

increased CD4-positive, alpha-beta T cell number ( J:146176 )

• CD44 high CD4+ T cells are increased in mice with hyperplasia or lymphomas

decreased lymphocyte cell number ( J:146176 )

• in spleens and lymph nodes

abnormal spleen morphology ( J:146743 )

• dark spleens

enlarged spleen ( J:146743 )

increased spleen red pulp amount ( J:146743 )

• due to increased erythroid and myeloid cells

enlarged lymph nodes ( J:146743 )

• 3 mice exhibit generalized lymphadenopathy characterized by non-specific, reactive lymphoid hyperplasia unlike in wild-type mice

lymphoid hyperplasia ( J:146176 )

• most mice succumb to splenic, lymph node, and thymic lymphomas and lymphoid hyperplasias by week 58

liver inflammation ( J:146743 )

• subacute

interstitial pneumonia ( J:146743 )

muscle

myocardial fiber degeneration ( J:146743 )

• primarily involving the left ventricular free wall and septum

cardiomyopathy ( J:146743 )

skeleton

kyphosis ( J:146176 , J:146743 )

• at 8 to 10 months of age (J:146176)

• as early as 16 weeks of age (J:146743)

lordosis ( J:146176 )

• at 8 to 10 months of age

neoplasm

increased lymphoma incidence ( J:146176 )

• lymphomas are first observed at 26 weeks of age

• most mice succumb to splenic, lymph node, and thymic lymphomas and lymphoid hyperplasias by week 58

increased T cell derived lymphoma incidence ( J:146176 )

endocrine/exocrine glands

bile duct hyperplasia ( J:146743 )

• minimal to mild

increased T cell derived lymphoma incidence ( J:146176 )

integument

disheveled coat ( J:146743 )

• as early as 16 weeks of age, mice have scruffy coats unlike wild-type mice

Genotype
MGI:5515353

ht4

• Allelic Composition: Chd2^{Gt(RRBO46)Byg}/Chd2⁺
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6J

mortality/aging

preweaning lethality, incomplete penetrance ( J:137079 )

• fewer than expected mice are present at weaning

reproductive system

uterus cyst ( J:137079 )

♀ • cystic endometrial hyperplasia in 3 of 8 female mice

endometrium hyperplasia ( J:137079 )

♀ • cystic endometrial hyperplasia in 3 of 8 female mice

adipose tissue

absent subcutaneous adipose tissue ( J:137079 )

• absent or extremely hypoplastic

decreased subcutaneous adipose tissue amount ( J:137079 )

• absent or extremely hypoplastic

cardiovascular system

abnormal blood vessel morphology ( J:137079 )

• filling defects in the distal vasculature of the distal extremities

increased heart atrium size ( J:137079 )

• mild to moderate in some neonates

growth/size/body

uterus cyst ( J:137079 )

♀ • cystic endometrial hyperplasia in 3 of 8 female mice

decreased body size ( J:137079 )

postnatal growth retardation ( J:137079 )

integument

absent subcutaneous adipose tissue ( J:137079 )

• absent or extremely hypoplastic

decreased subcutaneous adipose tissue amount ( J:137079 )

• absent or extremely hypoplastic

renal/urinary system

cortical renal glomerulopathies ( J:137079 )

• glomerulonephropathy in 15 of 32 adult mice

• however, neonatal mice exhibit normal renal histopathology

skeleton

lordokyphosis ( J:137079 )

• lordokyphosis at 4 months

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
CHARGE syndrome		DOID:0050834	OMIM:214800	J:137079