Phenotypes associated with this allele

• Allele Symbol: Sptbn1^tm1Mish
• Allele Name: targeted mutation 1, Lopa Mishra
• Allele ID: MGI:2450327
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Sptbn1^tm1Mish/Sptbn1^tm1Mish	either: (involves: 129S6/SvEvTac * C57BL/6) or (involves: 129S6/SvEvTac * NIH Black Swiss)	MGI:2450867
ht2	Sptbn1^tm1Mish/Sptbn1^+	involves: 129S6/SvEvTac	MGI:4936861
ht3	Sptbn1^tm1Mish/Sptbn1^+	involves: 129S6/SvEvTac * C57BL/6	MGI:3783627
cx4	Itih4^tm1Mish/Itih4^tm1Mish Sptbn1^tm1Mish/Sptbn1^+	involves: 129S6/SvEvTac * C57BL/6 * NIH Black Swiss	MGI:3783628

Genotype
MGI:2450867

hm1

• Allelic Composition: Sptbn1^tm1Mish/Sptbn1^tm1Mish
• Genetic Background: either: (involves: 129S6/SvEvTac * C57BL/6) or (involves: 129S6/SvEvTac * NIH Black Swiss)

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

mortality/aging

lethality throughout fetal growth and development, complete penetrance ( J:81747 )

• abnormal or degenerating embryos detected between E8.5 and E16.5

cardiovascular system

abnormal vitelline vasculature morphology ( J:81747 )

• lack of branching network of vessels in yolk sac

abnormal myocardial fiber morphology ( J:81747 )

• absence of trabeculated pattern of myocardial tissue; myoblasts were hyperplastic and lacked linear arrangement of nuclei

abnormal heart ventricle morphology ( J:81747 )

• small ventricular lumen; occlusion of atrioventricular region

craniofacial

abnormal craniofacial morphology ( J:81747 )

digestive/alimentary system

abnormal digestive system morphology ( J:81747 )

• aberrant gut formation

embryo

abnormal vitelline vasculature morphology ( J:81747 )

• lack of branching network of vessels in yolk sac

decreased embryo size ( J:81747 )

• smaller body and head size, evident at E9.5

growth/size/body

decreased embryo size ( J:81747 )

• smaller body and head size, evident at E9.5

liver/biliary system

abnormal liver morphology ( J:81747 )

• distorted architecture

liver hypoplasia ( J:81747 )

muscle

abnormal myocardial fiber morphology ( J:81747 )

• absence of trabeculated pattern of myocardial tissue; myoblasts were hyperplastic and lacked linear arrangement of nuclei

nervous system

abnormal brain development ( J:81747 )

• abnormal anatomy of primary brain vesicles

Genotype
MGI:4936861

ht2

• Allelic Composition: Sptbn1^tm1Mish/Sptbn1⁺
• Genetic Background: involves: 129S6/SvEvTac

Beckwith-Wiedemann Syndrome-like phenotypes in Sptbn1^tm1Mish/Spnb2⁺ mice

mortality/aging

premature death ( J:166879 )

• increase in incidence of sudden death in males

growth/size/body

enlarged heart ( J:166879 )

• cardiomegaly

increased tongue size ( J:166879 )

• macroglossia

abnormal outer ear morphology ( J:166879 )

• multiple ear folds

adrenal gland cyst ( J:166879 )

• adrenal cysts

increased body size ( J:166879 )

• 25% increase in average body size and mass compared to wild-type

enlarged kidney ( J:166879 )

• renal hypertrophy

visceromegaly ( J:166879 )

• visceromegaly

neoplasm

increased adrenal cortical tumor incidence ( J:166879 )

• adrenocortical carcinomas

increased ovary tumor incidence ( J:166879 )

♀ • 3.4% incidence of epithelial tumors in the ovary

increased testis tumor incidence ( J:166879 )

♂ • 3.4% incidence of testicular carcinomas

increased liver tumor incidence ( J:166879 )

• 37.9-40% increase in incidence of liver tumors

increased hepatocellular carcinoma incidence ( J:166879 )

increased adenoma incidence ( J:166879 )

• 3.4% incidence of breast adenomas

increased lymphoma incidence ( J:166879 )

• 6.9% incidence of spleen lymphomas

increased carcinoma incidence ( J:166879 )

• pancreatic carcinomas and adrenocortical carcinomas

• 3.4% incidence of testicular carcinomas

increased thyroid carcinoma incidence ( J:166879 )

increased lung adenocarcinoma incidence ( J:166879 )

• 6.9% incidence of adenocarcinomas in the lung

increased renal carcinoma incidence ( J:166879 )

• 10.3% incidence of renal cell carcinomas

increased sarcoma incidence ( J:166879 )

• 3.4% incidence of abdominal/mesenchymal sarcomas

increased glioma incidence ( J:166879 )

• optic nerve gliomas

hearing/vestibular/ear

abnormal outer ear morphology ( J:166879 )

• multiple ear folds

integument

alopecia ( J:166879 )

• frontal balding

cardiovascular system

enlarged heart ( J:166879 )

• cardiomegaly

craniofacial

increased tongue size ( J:166879 )

• macroglossia

abnormal outer ear morphology ( J:166879 )

• multiple ear folds

digestive/alimentary system

increased tongue size ( J:166879 )

• macroglossia

endocrine/exocrine glands

adrenal gland cyst ( J:166879 )

• adrenal cysts

increased adrenal cortical tumor incidence ( J:166879 )

• adrenocortical carcinomas

increased thyroid carcinoma incidence ( J:166879 )

increased ovary tumor incidence ( J:166879 )

♀ • 3.4% incidence of epithelial tumors in the ovary

enlarged testis ( J:166879 )

♂

increased testis tumor incidence ( J:166879 )

♂ • 3.4% incidence of testicular carcinomas

liver/biliary system

abnormal liver morphology ( J:166879 )

• multilobed livers

increased liver tumor incidence ( J:166879 )

• 37.9-40% increase in incidence of liver tumors

increased hepatocellular carcinoma incidence ( J:166879 )

renal/urinary system

enlarged kidney ( J:166879 )

• renal hypertrophy

increased renal carcinoma incidence ( J:166879 )

• 10.3% incidence of renal cell carcinomas

reproductive system

increased ovary tumor incidence ( J:166879 )

♀ • 3.4% incidence of epithelial tumors in the ovary

enlarged testis ( J:166879 )

♂

increased testis tumor incidence ( J:166879 )

♂ • 3.4% incidence of testicular carcinomas

respiratory system

increased lung adenocarcinoma incidence ( J:166879 )

• 6.9% incidence of adenocarcinomas in the lung

nervous system

increased glioma incidence ( J:166879 )

• optic nerve gliomas

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Beckwith-Wiedemann syndrome		DOID:5572	OMIM:130650	J:166879

Genotype
MGI:3783627

ht3

• Allelic Composition: Sptbn1^tm1Mish/Sptbn1⁺
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6

neoplasm

increased hepatocellular carcinoma incidence ( J:132133 )

• mice spontaneously develop tumors of the liver with an incidence of 40%

• lesions included early centrilobular steatosis and dysplasia with nuclear disarray and stratification

• many of these lesions progress to poorly differentiated carcinomas

liver/biliary system

decreased hepatocyte proliferation ( J:132133 )

• apoptosis rates are lower among hepatocytes potentially leading to lesion formation

increased hepatocellular carcinoma incidence ( J:132133 )

• mice spontaneously develop tumors of the liver with an incidence of 40%

• lesions included early centrilobular steatosis and dysplasia with nuclear disarray and stratification

• many of these lesions progress to poorly differentiated carcinomas

cellular

decreased hepatocyte proliferation ( J:132133 )

• apoptosis rates are lower among hepatocytes potentially leading to lesion formation

Genotype
MGI:3783628

cx4

• Allelic Composition: Itih4^tm1Mish/Itih4^tm1Mish; Sptbn1^tm1Mish/Sptbn1⁺
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * NIH Black Swiss

neoplasm

decreased liver tumor incidence ( J:132133 )

• only 1 mouse in 25 developed a liver neoplasm compared to the 40% incidence rate observed in mice carrying just one null allele for Spnb2

• the lone tumor was about 10-fold smaller than the mean tumor sizes observed in the control mice

liver/biliary system

decreased hepatocyte apoptosis ( J:132133 )

• apoptosis rates are lower in hepatocytes compared to control mice

decreased hepatocyte proliferation ( J:132133 )

• hepatocyte proliferation is lower than in controls

decreased liver tumor incidence ( J:132133 )

• only 1 mouse in 25 developed a liver neoplasm compared to the 40% incidence rate observed in mice carrying just one null allele for Spnb2

• the lone tumor was about 10-fold smaller than the mean tumor sizes observed in the control mice

cellular

decreased hepatocyte apoptosis ( J:132133 )

• apoptosis rates are lower in hepatocytes compared to control mice

decreased hepatocyte proliferation ( J:132133 )

• hepatocyte proliferation is lower than in controls