Phenotypes Associated with This Genotype

Genotype
MGI:8175487

• Allelic Composition: Dnmt3a^em1Hwg/Dnmt3a⁺
• Genetic Background: B6.Cg-Dnmt3a^em1Hwg

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

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 tibia ( J:348991 )

♀ • females exhibit a significant increase in tibial length at 30 to 36 weeks of age

growth/size/body

increased body fat mass ( J:348795 )

• aged mice exhibit increased fat mass

obese ( J:348795 )

• mice show increased body weight trends at 30-35 weeks and increased fat mass with no change in lean mass, indicating obesity

increased susceptibility to diet-induced obesity ( J:348795 )

• mice exhibit increased weight gain on a high-fat diet

• however, no increase in food consumption is seen

adipose tissue

increased body fat mass ( J:348795 )

• aged mice exhibit increased fat mass

behavior/neurological

behavior/neurological phenotype ( J:348795 )

N • mice show normal open field activity, marble burying, motor, coordination, and sensorimotor phenotypes, anxiety-like phenotypes, responses to aversive stimuli and contextual and cued fear memory, spatial learning in the Morris water maze, social preference or novelty, and social dominance or hierarchies

abnormal response to novel object ( J:348795 )

• in the novel object recognition task in which mice explore objects that are visually indistinguishable but differ in texture, mice do not show a preference to explore a novel tactile object as is seen in wild-type mice

• however, mice display similar novel object preference for visually and physically distinct objects as wild-type mice, indicating a specific tactile discrimination defect and not broad deficits in associative memory or novelty-seeking behaviors

decreased vocalization ( J:348795 )

• pups make fewer calls when removed from the nest, indicating a deficit in early communication

craniofacial

abnormal cranium morphology ( J:348795 )

• mice show a few subtle changes in distances between skull Euclidian landmarks

• however, no increase in skull size is observed

homeostasis/metabolism

increased susceptibility to diet-induced obesity ( J:348795 )

• mice exhibit increased weight gain on a high-fat diet

• however, no increase in food consumption is seen

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 and no changes in corpus callosum size or ventricular volume are seen

decreased brain size ( J:348795 )

abnormal brain white matter morphology ( J:348795 )

• subtle, but significant, decrease in the fractional anisotropy of the MRI, indicating changes in white matter integrity or organization

thin cerebral cortex ( J:348795 )

• aged mice show broad reductions in cortical thickness

skeleton

abnormal cranium morphology ( J:348795 )

• mice show a few subtle changes in distances between skull Euclidian landmarks

• however, no increase in skull size is observed

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

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

increased length of long bones ( J:348795 )

• femurs are longer indicating increased long bone length

long tibia ( J:348991 )

♀ • females exhibit a significant increase in tibial length at 30 to 36 weeks of age

abnormal skeleton physiology ( J:348991 )

• when normalized to the femoral mid-diaphysis cross-sectional area, 30- to 36-week-old mice exhibit reduced Youngs modulus, yield stress, and ultimate stress

• however, no change is seen in osteoclast number or osteoclast surface per bone surface on the endocortical surface of juvenile femur mid-diaphysis and no change is seen in bone formation indices, suggesting no difference in osteoblast activity, and no change is seen in mineral apposition rate and mineralizing surface per bone surface values

decreased bone stiffness ( J:348991 )

• seen in 30- to 36-week-old femurs, with females showing a greater effect than males

decreased femur maximal load ( J:348991 )

• seen in 30- to 36-week-old femurs, with females showing a greater effect than males

• however, post-yield displacement and work-to-fracture remains the same suggesting that brittleness of bones is unchanged

decreased femur yield load ( J:348991 )

• seen in 30- to 36-week-old femurs, with females showing a greater effect than males

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