Phenotypes associated with this allele

• Allele Symbol: Crebbp^tm1Sis
• Allele Name: targeted mutation 1, Shunsuke Ishii
• Allele ID: MGI:1928768
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Crebbp^tm1Sis/Crebbp^tm1Sis	involves: BALB/cCrSlc * C57BL/6NCrlj * CBA/JNCrlj	MGI:3588515
ht2	Crebbp^tm1Sis/Crebbp^+	involves: BALB/cCrSlc * C57BL/6NCrlj * CBA/JNCrlj	MGI:3588514
ht3	Crebbp^tm1Sis/Crebbp^+	involves: C57BL/6NCrlj * CBA/JNCrlj	MGI:2175796

Genotype
MGI:3588515

hm1

• Allelic Composition: Crebbp^tm1Sis/Crebbp^tm1Sis
• Genetic Background: involves: BALB/cCrSlc * C57BL/6NCrlj * CBA/JNCrlj

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

mortality/aging

embryonic lethality, complete penetrance ( J:42932 )

• die between E8 and E10

embryonic lethality during organogenesis, complete penetrance ( J:63763 )

• homozygotes die at E10.5-E11.5 from massive brain hemorrhage; no homozygotes survive beyond E12.5

nervous system

intracranial hemorrhage ( J:63763 )

• at E10.5 and E11.5, homozygotes exhibit severe hemorrhage in the telencephalon and mesencephalon and segmental bleeding in areas corresponding to the VII/VIII cranial nerve complex

abnormal neural tube morphology ( J:63763 )

• at E10.5, the neural tube shows aberrant morphology due to cellular invasion into the neural lumen

• in some cases, eversion of the neural tissue from the telencephalon to the myelencephalon is observed

incomplete rostral neuropore closure ( J:63763 )

• at E10.5, homozygotes display defective neural tube closure: the cranial neural folds are elevated and approach each other medially but fail to initiate fusion

open neural tube ( J:63763 )

• in some cases, the neural tube remains open on the dorsal side with a low degree of eversion of neural tissue

abnormal forebrain morphology ( J:63763 )

• at E10.5, mutant forebrains show reduced mesenchymal cell density with less intercellular contacts and enlarged extracellular spaces

exencephaly ( J:63763 )

• at E10.5, homozygotes exhibit exencephaly

abnormal spinal cord morphology ( J:63763 )

• at E10.5, the spinal cord of homozygotes lacks cellular organization and displays eversion of neural tissue

• at E11.5, the density of neuroepithelial cells is reduced

cardiovascular system

abnormal blood vessel morphology ( J:63763 )

• at E10.5 and E11.5, the structure of blood vessels in everted neural tissue is highly abnormal and vascularity is reduced

decreased angiogenesis ( J:63763 )

abnormal vasculogenesis ( J:63763 )

• homozygotes display abnormal vasculogenesis; however, neither defects in heart morphogenesis nor heart beat anomalies are observed

intracranial hemorrhage ( J:63763 )

• at E10.5 and E11.5, homozygotes exhibit severe hemorrhage in the telencephalon and mesencephalon and segmental bleeding in areas corresponding to the VII/VIII cranial nerve complex

embryo

embryonic growth retardation ( J:63763 )

• at E9.5, homozygotes display an obvious developmental delay in the absence of gross abnormalities

decreased embryo size ( J:63763 )

• at E10.5, the size of homozygous mutant embryos is ~70% that of wild-type embryos

abnormal neural tube morphology ( J:63763 )

• at E10.5, the neural tube shows aberrant morphology due to cellular invasion into the neural lumen

• in some cases, eversion of the neural tissue from the telencephalon to the myelencephalon is observed

incomplete rostral neuropore closure ( J:63763 )

• at E10.5, homozygotes display defective neural tube closure: the cranial neural folds are elevated and approach each other medially but fail to initiate fusion

open neural tube ( J:63763 )

• in some cases, the neural tube remains open on the dorsal side with a low degree of eversion of neural tissue

abnormal extraembryonic tissue morphology ( J:63763 )

• at E10.5, homozygotes show abnormalities in the mesenchymal region of the forebrain and trunk: mesenchymal cell density is reduced with less intercellular contacts and enlarged extracellular spaces

pale yolk sac ( J:63763 )

• at E10.5, mutant yolk sac are pale due to a significant reduction in circulating erythrocytes

hematopoietic system

impaired hematopoiesis ( J:63763 )

• at E9.5 and E10.5, homozygotes exhibit a partial block in primitive and definitive hematopoiesis

• at E10.5, the total number of blood cells arising from mutant yolk sacs is 46-77% that of wild-type yolk sacs whereas the total number of hematopoietic progenitor cells present in mutant embryo bodies is 26-53% of wild-type

• comparison of the number of hematopoietic progenitor cells at E9.5 and E10.5 suggest a delay in hematopoiesis

growth/size/body

embryonic growth retardation ( J:63763 )

• at E9.5, homozygotes display an obvious developmental delay in the absence of gross abnormalities

decreased embryo size ( J:63763 )

• at E10.5, the size of homozygous mutant embryos is ~70% that of wild-type embryos

integument

pallor ( J:63763 )

• at E10.5, homozygoues embryos are quite pale in color

Genotype
MGI:3588514

ht2

• Allelic Composition: Crebbp^tm1Sis/Crebbp⁺
• Genetic Background: involves: BALB/cCrSlc * C57BL/6NCrlj * CBA/JNCrlj

cardiovascular system

cardiovascular system phenotype ( J:42932 , J:63763 )

• heterozygotes do not exhibit any of the cardiac anomalies observed in Rubinstein-Taybi Syndrome (J:42932)

• heterozygotes do not exhibit any of the cardiac anomalies observed in Rubinstein-Taybi Syndrome (J:63763)

mortality/aging

prenatal lethality, incomplete penetrance ( J:42932 , J:63763 )

• a small subset of heterozygotes are embryonic lethal (J:42932)

• at 4 weeks of age, the ratio of wild-type:heterozygous genotypes is 1:1.2 (J:42932)

• a small subset of heterozygotes are embryonic lethal (J:63763)

• at 4 weeks of age, the ratio of wild-type:heterozygous genotypes is 1:1.2 (J:63763)

craniofacial

large anterior fontanelle ( J:42932 )

• Background Sensitivity: seen in 66% of heterozygotes on the mixed BALB/c, C57BL/6 and CBA background and in 25% of heterozygotes on a mixed C57BL/6 and CBA background

growth/size/body

postnatal growth retardation ( J:42932 )

• Background Sensitivity: 1/3 of heterozygotes exhibit growth retardation in the mixed BALB/c, C57BL/6, and CBA background while growth retardation is milder on the mixed C57BL/6 and CBA background

limbs/digits/tail

abnormal limb morphology ( J:42932 )

• low penetrance of limb abnormalities, however did not observe broad thumbs or broad halluces

skeleton

abnormal sternum morphology ( J:42932 )

• Background Sensitivity: 1/3 of heterozygotes exhibit various sternum abnormalities (extra, fusion, reduction, and asymmetry of the ossification with split in the sternum) on a mixed BALB/c, C57BL/6 and CBA background, while penetrance is significantly lower on the mixed C57BL/6 and CBA background

xiphoid process foramen ( J:42932 )

• Background Sensitivity: 29% of heterozygotes on the mixed BALB/c, C57BL/6, and CBA background exhibit distinct holes and fissures in the xiphoid process while 66% of heterozygotes on the mixed C57BL/6 and CBA background display xiphoid defects

abnormal rib morphology ( J:42932 )

• low frequency of rib abnormalities

scoliosis ( J:42932 )

• incomplete penetrance on the mixed BALB/c, C57BL/6, and CBA background

abnormal vertebrae morphology ( J:42932 )

• asymmetric cervical vertebrae, extra and split thoracic vertebrae, and scoliosis are observed on the mixed BALB/c, C57BL/6, and CBA background

abnormal joint morphology ( J:42932 )

• 1/3 of heterozygotes on a mixed BALB/c, C57BL/6 and CBA background have asymmetric sternocostal joints

large anterior fontanelle ( J:42932 )

• Background Sensitivity: seen in 66% of heterozygotes on the mixed BALB/c, C57BL/6 and CBA background and in 25% of heterozygotes on a mixed C57BL/6 and CBA background

delayed bone ossification ( J:42932 )

• delayed ossification of frontal bones on a mixed BALB/c, C57BL/6 and CBA background

Genotype
MGI:2175796

ht3

• Allelic Composition: Crebbp^tm1Sis/Crebbp⁺
• Genetic Background: involves: C57BL/6NCrlj * CBA/JNCrlj

Skeletal formation defects in Crebbp^tm1Sis/Crebbp⁺ mice

growth/size/body

postnatal growth retardation ( J:42932 )

• Background Sensitivity: growth retardation is milder than in mice on a background containing BALB/c

skeleton

large anterior fontanelle ( J:42932 )

• Background Sensitivity: in 25% of mice compared to in 66% of heterozygotes on a background containing BALB/c

abnormal sternum morphology ( J:42932 )

• Background Sensitivity: at a much lower than in mice on a background containing BALB/c

xiphoid process foramen ( J:42932 )

• Background Sensitivity: in 16 of 24 mice, more frequent than in mice on a background containing BALB/c

craniofacial

large anterior fontanelle ( J:42932 )

• Background Sensitivity: in 25% of mice compared to in 66% of heterozygotes on a background containing BALB/c

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Rubinstein-Taybi syndrome		DOID:1933	OMIM:180849 OMIM:610543 OMIM:613684	J:42932