Phenotypes Associated with This Genotype

Genotype
MGI:7488670

• Allelic Composition: Chd7^Gt(XK403)Byg/Chd7⁺
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * DBA/2

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

nervous system

abnormal cerebellar foliation ( J:262209 )

• 64% of adult mice exhibit a subtle cerebellar foliation anomaly, with variable severity between individual mice

• most pronounced foliation anomaly involves a small and posteriorly shifted lobule VIII associated with a shallow secondary fissure

• foliation defects result from defects in the timing and position of fissure formation during cerebellar development

• however, remaining 36% of mice exhibit a normal foliation structure

decreased brain size ( J:262209 )

• adult mice (~P60) show a 9% reduction in mean total brain volume

abnormal cerebral cortex morphology ( J:262209 )

• adult mice show a 9.7% reduction in mean total cortical volume

abnormal cerebellar hemisphere morphology ( J:262209 )

• mice that exhibit foliation defects in the vermis also show a hemisphere-specific foliation defect; overall penetrance of this foliation phenotype in the hemispheres is also 67%

abnormal cerebellum hemisphere lobule morphology ( J:262209 )

abnormal lobule simplex morphology ( J:262209 )

• adult mice show a 15% reduction of simplex lobule in the anterior hemisphere of the cerebellum

• delayed formation of the superior posterior fissure results in a shallower fissure at later stages, incomplete separation of the simplex and Crus I lobules and hypoplasia of the simplex lobule

abnormal cerebellum fissure morphology ( J:262209 )

• mildly affected mice exhibit a deeper prepyramidal fissure and a correspondingly shallower secondary fissure, resulting in a subtle posterior shift of lobule VIII

• severely affected mice show a markedly smaller and even more posteriorly shifted lobule VIII associated with a shallow secondary fissure

• in some mice, the superior posterior fissure that separates the simplex lobule from Crus I appears to be shallower, leading to partial fusion of these lobules in the anterior cerebellar hemispheres

• at E18.5, mice show a general delay in fissure formation in the vermis, with shallower preculminate and primary fissures and absence of the secondary and posterolateral fissures

• at E18.5 and P0, 60% of mice show defects in fissure formation in the vermis, in agreement with the incidence foliation defects in adult mice; formation of the preculminate, primary, secondary, and posterolateral fissures is delayed while the prepyramidal fissure is shifted to a more posterior position

• similar to findings in the vermis, delayed fissure formation is seen in the hemispheres at P2; formation of the superior posterior fissure is specifically delayed, resulting in a shallower fissure at later stages, incomplete separation of the simplex and Crus I lobules and hypoplasia of the simplex lobule

abnormal cerebellum vermis lobule morphology ( J:262209 )

abnormal cerebellum vermis lobule VIII morphology ( J:262209 )

• adult mice show a 16% reduction of lobule VIII in the posterior vermis of the cerebellum

• at P21, three of 7 mice show a small posterior shift of lobule VIII along lobule IX, while 2 of 7 mice show a more pronounced shift of lobule VIII accompanied by hypoplasia

• total incidence of foliation change affecting lobule VIII in the vermis is 67% (12 of 18)

small cerebellum ( J:262209 )

• adult mice show a ~12% reduction in mean total cerebellar volume

• severely affected mice show a 17% in mean cerebellar volume

cerebellum hypoplasia ( J:262209 )

• ~65% (12 of 18) mice exhibit mild, but significant, cerebellar hypoplasia

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
CHARGE syndrome		DOID:0050834	OMIM:214800	J:262209