Phenotypes associated with this allele

• Allele Symbol: Dnmt3a^tm1.1Rlvn
• Allele Name: targeted mutation 1.1, Ross Levine
• Allele ID: MGI:8175499
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Dnmt3a^tm1.1Rlvn/Dnmt3a^tm1.1Rlvn	B6(C)-Dnmt3a^tm1.1Rlvn	MGI:8175638
ht2	Dnmt3a^tm1.1Rlvn/Dnmt3a^+	B6(C)-Dnmt3a^tm1.1Rlvn	MGI:8175639

Genotype
MGI:8175638

hm1

• Allelic Composition: Dnmt3a^tm1.1Rlvn/Dnmt3a^tm1.1Rlvn
• Genetic Background: B6(C)-Dnmt3a^tm1.1Rlvn

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

growth/size/body

decreased birth body size ( J:321204 )

• mice are severely runted at birth

mortality/aging

postnatal lethality, complete penetrance ( J:321204 )

• mice do not survive past 1 week of age

Genotype
MGI:8175639

ht2

• Allelic Composition: Dnmt3a^tm1.1Rlvn/Dnmt3a⁺
• Genetic Background: B6(C)-Dnmt3a^tm1.1Rlvn

adipose tissue

increased total body fat amount ( J:321204 )

• age-dependent increase in body fat, but not lean mass

• however, food consumption is not increased

abnormal bone marrow adipose tissue morphology ( J:348991 )

• cross-sectional area of bone marrow adipocytes in the tibia proximal metaphysis is increased

• 22% of female mice show a robust increase in adipocyte volume in the tibia proximal metaphysis

nervous system

abnormal brain morphology ( J:348795 )

• aged mice (30-35 weeks) show reduced brain volume, however brain volume is normal at P10 and 8 weeks of age and cerebral volume and cell counts are normal at 8 weeks of age

decreased brain size ( J:348795 )

abnormal brain ventricle morphology ( J:348795 )

• aged mice exhibit subtle reductions in ventricular volume

thin cerebral cortex ( J:348795 )

• aged mice show broad reductions in cortical thickness

behavior/neurological

behavior/neurological phenotype ( J:321204 )

N • mice show no difference in sensorimotor behavior, such as balance, walking initiation, grip strength, and motor coordination, and in intellectual disability, memory or anxiety tests, including the elevated plus maze, Morris water maze test, and probe trial

abnormal associative learning ( J:348795 )

• tactile discrimination assays show no preference for novel tactile objects and no preference for visually distinct novel objects indicating a possible broad disruption of associative learning and memory

enhanced contextual conditioning behavior ( J:321204 )

• mice show increased time spent freezing in contextual fear testing

enhanced cued conditioning behavior ( J:321204 )

• mice show increased time spent freezing in cued fear testing

decreased food intake ( J:321204 )

• mice eat less chow than wild-type mice

abnormal response to novel object ( J:348795 )

• tactile discrimination assays show no preference for novel tactile objects and no preference for visually distinct novel objects indicating a possible broad disruption of associative learning and memory

abnormal motor capabilities/coordination/movement ( J:321204 )

• mice take longer to climb down a pole and more time to climb-up an inclined screen

hypoactivity ( J:321204 )

• 100- to 200-day old mice show reduced total ambulations in open field tests

decreased vertical activity ( J:321204 )

• 100-to 200-day old mice show reduced rearing events in open field tests

increased stereotypic behavior ( J:321204 )

• mice exhibit reduced marble-burying

abnormal social/conspecific interaction behavior ( J:348795 )

• mice show changes in social hierarchies, winning more bouts in the tube test

decreased vocalization ( J:348795 )

• ultrasonic vocalizations are reduced in pups that are removed from the nest

craniofacial

abnormal cranium morphology ( J:321204 )

• some features of skulls are slightly larger, including the mandible and localized structures in the cranium

• however, no difference in head circumference (length and width of the neurocranial bones) is seen

large mandible ( J:321204 )

• mandible is slightly larger

growth/size/body

decreased lean body mass ( J:348991 )

• juvenile mice (21 to 27 days of age) exhibit a small reduction lean mass

decreased body weight ( J:348991 )

• juvenile mice (21 to 27 days of age) exhibit a small reduction in body weight and decreased lean mass

increased susceptibility to diet-induced obesity ( J:321204 )

• obesity is exacerbated by high-fat diet feeding

increased body size ( J:321204 )

• mice show increased size at 1 year of age, however size at birth and before 100 days of age is normal

increased body weight ( J:321204 , J:348991 )

• mice show increased weight with age, however weight at birth and before 100 days of age is normal (J:321204)

• 30- to 36-week old mice exhibit an increase in body weight under normal chow feeding conditions (J:348991)

obese ( J:321204 )

• age-dependent increase in body fat, but not lean mass, indicating obesity

increased body height ( J:321204 )

• 210-day-old mice show longer femur lengths but not humerus lengths, indicating increased height

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:321204 )

N • plasma levels of leptin, triglycerides, cholesterol, glucose, and free fatty acids are not different in fasted mice

increased susceptibility to diet-induced obesity ( J:321204 )

• obesity is exacerbated by high-fat diet feeding

decreased respiratory quotient ( J:321204 )

• mice over 6 months of age, but not under 6 months, show a non-significant decrease in O2 consumption and a significant decrease in CO2 production, suggesting a slight decrease in respiratory quotient

limbs/digits/tail

decreased femur compact bone thickness ( J:348991 )

• femoral and tibial mid-diaphysis cortical bone thickness is reduced in 30- to 36-week-old mice

• however, cortical tissue mineral density, marrow volume, and total volume are unchanged and no differences in femoral trabecular bone volume per tissue volume is seen

long femur ( J:321204 )

• in 210-day-old mice

abnormal tibia morphology ( J:348991 )

♀ • females show a reduction in tibia marrow volume and total volume

♀ • 22% of female mice show a robust increase in adipocyte volume in the tibia proximal metaphysis

long tibia ( J:348991 )

• mice exhibit a small significant increase in tibial length at 30 to 36 weeks of age

neoplasm

increased classified tumor incidence ( J:321204 )

• 6 of 80 mice develop spontaneous, fatal hematopoietic malignancies after 1 year of age, including ones classified as myelodysplastic syndrome with maturation, B-cell malignancies with extensive plasma cells in the bone marrow and spleen, one acute myeloid leukemia without differentiation and one chronic myelomonocytic leukemia-like disease

• however, very few perturbations in mature cell populations in the peripheral blood and bone marrow (B-, T-, erythroid and myeloid cells), stem populations, or progenitor populations and hematopoietic cells do not show defects following the stress of a cytotoxic challenge with doxorubicin and cytarabine

increased leukemia incidence ( J:321204 )

• 1 of 80 mice developed chronic myelomonocytic leukemia-like disease

increased acute myeloid leukemia incidence ( J:321204 )

• 1 of 80 mice developed acute myeloid leukemia without differentiation

reproductive system

dystocia ( J:321204 )

♀ • females have a significant incidence of dystocia during pregnancy

skeleton

abnormal bone marrow adipose tissue morphology ( J:348991 )

• cross-sectional area of bone marrow adipocytes in the tibia proximal metaphysis is increased

• 22% of female mice show a robust increase in adipocyte volume in the tibia proximal metaphysis

abnormal cranium morphology ( J:321204 )

• some features of skulls are slightly larger, including the mandible and localized structures in the cranium

• however, no difference in head circumference (length and width of the neurocranial bones) is seen

large mandible ( J:321204 )

• mandible is slightly larger

decreased femur compact bone thickness ( J:348991 )

• femoral and tibial mid-diaphysis cortical bone thickness is reduced in 30- to 36-week-old mice

• however, cortical tissue mineral density, marrow volume, and total volume are unchanged and no differences in femoral trabecular bone volume per tissue volume is seen

long femur ( J:321204 )

• in 210-day-old mice

abnormal tibia morphology ( J:348991 )

♀ • females show a reduction in tibia marrow volume and total volume

♀ • 22% of female mice show a robust increase in adipocyte volume in the tibia proximal metaphysis

long tibia ( J:348991 )

• mice exhibit a small significant increase in tibial length at 30 to 36 weeks of age

increased long bone epiphyseal plate size ( J:348991 )

• growth plates in the proximal tibias of juvenile mice are slightly thicker; increase in thickness is not specific to the resting zone, proliferating zone, or hypertrophic zone

• only a slight trend towards growth plate thickening is seen in the distal femur of juveniles

abnormal bone marrow cavity morphology ( J:348991 )

♀ • females show a reduction in tibia marrow volume and total volume

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Tatton-Brown-Rahman syndrome		DOID:0112339	OMIM:615879	J:321204 , J:348795 , J:348991