Phenotypes associated with this allele

• Allele Symbol: Arid1b^em1Hzhu
• Allele Name: endonuclease-mediated mutation 1, Hao Zhu
• Allele ID: MGI:6116819
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Arid1b^em1Hzhu/Arid1b^em1Hzhu	C57BL/6J-Arid1b^em1Hzhu	MGI:6159714
ht2	Arid1b^em1Hzhu/Arid1b^+	C57BL/6J-Arid1b^em1Hzhu	MGI:6159715

Genotype
MGI:6159714

hm1

• Allelic Composition: Arid1b^em1Hzhu/Arid1b^em1Hzhu
• Genetic Background: C57BL/6J-Arid1b^em1Hzhu

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

mortality/aging

perinatal lethality, complete penetrance ( J:256668 )

• homozygotes are born but die perinatally

growth/size/body

decreased birth body size ( J:256668 )

• P0 homozygotes are significantly smaller than wild-type controls

Genotype
MGI:6159715

ht2

• Allelic Composition: Arid1b^em1Hzhu/Arid1b⁺
• Genetic Background: C57BL/6J-Arid1b^em1Hzhu

growth/size/body

decreased body size ( J:256668 )

• heterozygotes survive into adulthood and appear healthy but are small for age

decreased body weight ( J:256668 )

• heterozygotes show decreased body weight with no apparent changes in food intake or water consumption

• after 40 days of treatment with recombinant mouse GH (rmGH), heterozygotes gain significantly more body weight than wild-type controls

• treatment with recombinant human IGF1 (rhIGF1) failed to rescue the body weight abnormality

decreased body length ( J:256668 )

• heterozygotes show reduced nose-to-rump length relative to wild-type controls

• after 40 days of treatment with recombinant mouse GH (rmGH), heterozygotes gain significantly more nose-to-rump length than wild-type controls

postnatal growth retardation ( J:256668 )

• growth retardation is reversed by exogenous GH supplementation

behavior/neurological

behavior/neurological phenotype ( J:256668 )

N • heterozygotes show no significant deficits in locomotor activity, memory and learning, or foot shock sensitivity relative to wild-type controls

increased anxiety-related response ( J:256668 )

• in the open field test, heterozygotes spend significantly more time in the periphery, avoiding the anxiety-provoking center

• in the elevated plus maze, heterozygotes spend more time in the anxiety-relieving, walled arms of the maze

• in the dark-light box test, male heterozygotes avoid exploring the brightly lit chamber

• treatment with either recombinant human IGF1 (rhIGF1) or recombinant mouse GH (rmGH) failed to rescue the anxiety behavioral phenotype, as measured in the elevated plus maze

abnormal response to social novelty ( J:256668 )

• heterozygotes spend significantly less time interacting with unfamiliar juvenile mice

increased grooming behavior ( J:256668 )

• heterozygotes show increased self-grooming behavior and, potentially as a result, bury less marbles than wild-type controls in the marble-burying test

decreased grip strength ( J:256668 )

• at baseline, both fore- and hindlimb grip strength is lower than that in wild-type controls

• after 40 days of treatment with rmGH, heterozygotes gain significantly more grip strength than wild-type controls

abnormal vocalization ( J:256668 )

• during separation of pups from dams at P4, ultrasonic vocalizations (USVs ) are longer in duration and have an abnormal pitch

• however, total number of USVs emitted is normal relative to wild-type controls

nervous system

hydrocephaly ( J:256668 )

• 6.6% of heterozygotes exhibit hydrocephalus

decreased corpus callosum size ( J:256668 )

• at P50, corpus callosum volume is significantly reduced

abnormal dentate gyrus subgranular zone morphology ( J:256668 )

• a reduction in proliferating cells is observed in the subgranular zone of the dentate gyrus, esp. in posterior regions

decreased dentate gyrus size ( J:256668 )

• at P50, dentate gyrus volume is significantly reduced

decreased cerebral cortex cell number ( J:256668 )

• decreased cortex thickness is accompanied by reduced TBR1+ neuronal cellularity (TBR1 is an early neuronal marker)

thin cerebral cortex ( J:256668 )

• heterozygous pups show decreased cortex thickness with reduced TBR1+ neuronal cellularity

decreased neuron number ( J:256668 )

• reduced cortical thickness is accompanied by reduced neuron numbers

abnormal hypothalamus physiology ( J:256668 )

• in the mediobasal hypothalamus, Ghrh mRNA levels are similar to those in wild-type controls, indicating a lack of appropriate GHRH response to the observed IGF1 deficiency

homeostasis/metabolism

abnormal homeostasis ( J:256668 )

• heterozygotes exhibit GHRH-GH-IGF1 axis deficiencies

abnormal insulin-like growth factor I level ( J:256668 )

• heterozygotes show a significant reduction in Igf1 mRNA levels in the liver, a major source of IGF1

decreased circulating insulin-like growth factor I level ( J:256668 )

• heterozygotes show a significant reduction in plasma IGF1 levels relative to wild-type controls

• however, fasting growth hormone (GH) levels and Gh mRNA expression in the pituitary are normal, and GH levels increase normally in response to exogenous growth hormone-releasing hormone (GHRH)

muscle

muscle weakness ( J:256668 )

• at P50, heterozygous exhibit muscle weakness, as shown by grip strength testing

• muscle strength is significantly improved by exogenous GH supplementation

cardiovascular system

small heart ( J:256668 )

• hearts are disproportionally small

decreased heart weight ( J:256668 )

• heart/body weight ratio is significantly lower than that in wild-type controls

renal/urinary system

small kidney ( J:256668 )

• kidneys are disproportionally small

decreased kidney weight ( J:256668 )

• kidney/body weight ratio is significantly lower than that in wild-type controls

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
autism spectrum disorder		DOID:0060041		J:256668
Coffin-Siris syndrome 1		DOID:0070042	OMIM:135900	J:256668