Phenotypes associated with this allele

• Allele Symbol: Men1^tm1Ctre
• Allele Name: targeted mutation 1, Judy S Crabtree
• Allele ID: MGI:2158697
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Men1^tm1Ctre/Men1^tm1Ctre	either: (involves: 129S6/SvEvTac * FVB/N) or (involves: 129S6/SvEvTac * Black Swiss * FVB/N)	MGI:3839764
ht2	Men1^tm1Ctre/Men1^+	either: (involves: 129S6/SvEvTac * FVB/N) or (involves: 129S6/SvEvTac * Black Swiss * FVB/N)	MGI:3839765
cn3	Men1^tm1Ctre/Men1^tm1Ctre Tg(Pdx1-cre)89.1Dam/0	involves: 129S6/SvEvTac * C57BL/6 * CBA * FVB/N	MGI:3843203
cn4	Men1^tm1Ctre/Men1^+ Tg(Pdx1-cre)89.1Dam/0	involves: 129S6/SvEvTac * C57BL/6 * CBA * FVB/N	MGI:3843204

Genotype
MGI:3839764

hm1

• Allelic Composition: Men1^tm1Ctre/Men1^tm1Ctre
• Genetic Background: either: (involves: 129S6/SvEvTac * FVB/N) or (involves: 129S6/SvEvTac * Black Swiss * FVB/N)

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

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:67128 )

• mice die prior to E14.5

embryo

embryonic growth retardation ( J:67128 )

• at E11.5 to E12.5

decreased embryo size ( J:67128 )

• at E11.5 to E12.5

craniofacial

abnormal craniofacial development ( J:67128 )

• in 20% of mice at E11.5 to E12.5

growth/size/body

embryonic growth retardation ( J:67128 )

• at E11.5 to E12.5

decreased embryo size ( J:67128 )

• at E11.5 to E12.5

Genotype
MGI:3839765

ht2

• Allelic Composition: Men1^tm1Ctre/Men1⁺
• Genetic Background: either: (involves: 129S6/SvEvTac * FVB/N) or (involves: 129S6/SvEvTac * Black Swiss * FVB/N)

neoplasm

increased stomach tumor incidence ( J:67128 )

• one mouse developed a gastric neuroendocrine tumor

increased adrenal gland tumor incidence ( J:67128 )

• 20% of mice develop adrenal cortical carcinomas

increased pheochromocytoma incidence ( J:67128 )

• in 7% of mice

increased pituitary adenoma incidence ( J:67128 )

• pituitary adenomas develop in 26% of mice by 16 months of age

• all pituitary tumors secrete prolactin but not ACTH

increased prolactinoma incidence ( J:67128 )

increased parathyroid adenoma incidence ( J:67128 )

• as early as 9 months, 24% of mice develop parathyroid adenomas compared to 2% of wild-type mice

increased thyroid adenoma incidence ( J:67128 )

• follicular adenoma

increased pancreas tumor incidence ( J:67128 )

• pancreatic islet cell tumors develop in 4 of 10 mice at 9 months of age unlike in wild-type mice

• by 16 months of age mice develop more numerous, large tumors

• at 22 months, one mouse exhibited capsular invasion

• by 22 months of age, 28% of mice exhibit pancreatic islet tumors unlike in wild-type mice

• pancreatic tumors begin at a slightly later age than in Men1^tm1.1Ctre heterozygotes

increased carcinoma incidence ( J:67128 )

• 20% of mice develop adrenal cortical carcinomas

increased lung adenocarcinoma incidence ( J:67128 )

• in 22% of mice

endocrine/exocrine glands

increased adrenal gland tumor incidence ( J:67128 )

• 20% of mice develop adrenal cortical carcinomas

increased pheochromocytoma incidence ( J:67128 )

• in 7% of mice

increased pituitary adenoma incidence ( J:67128 )

• pituitary adenomas develop in 26% of mice by 16 months of age

• all pituitary tumors secrete prolactin but not ACTH

increased prolactinoma incidence ( J:67128 )

increased parathyroid adenoma incidence ( J:67128 )

• as early as 9 months, 24% of mice develop parathyroid adenomas compared to 2% of wild-type mice

increased thyroid adenoma incidence ( J:67128 )

• follicular adenoma

thyroid gland cyst ( J:67128 )

• thyroid cysts

abnormal pancreas morphology ( J:67128 )

• some mice exhibit fatty replacement unlike wild-type mice

abnormal pancreatic acinar cell morphology ( J:67128 )

• some mice exhibit duct inflammation, acinar cysts, focal acinar dysplasia, and focal acinar necrosis unlike wild-type mice

pancreatic islet hyperplasia ( J:67128 )

• in 4 of 10 mice at 9 months of age

increased pancreas tumor incidence ( J:67128 )

• pancreatic islet cell tumors develop in 4 of 10 mice at 9 months of age unlike in wild-type mice

• by 16 months of age mice develop more numerous, large tumors

• at 22 months, one mouse exhibited capsular invasion

• by 22 months of age, 28% of mice exhibit pancreatic islet tumors unlike in wild-type mice

• pancreatic tumors begin at a slightly later age than in Men1^tm1.1Ctre heterozygotes

pancreas cyst ( J:67128 )

• acinar cysts in some mice

pancreas necrosis ( J:67128 )

• focal acinar necrosis in some mice

pancreas inflammation ( J:67128 )

• some mice exhibit duct inflammation in the pancreas

homeostasis/metabolism

increased circulating insulin level ( J:67128 )

• in mice with islet hypoplasia and/or pancreatic islet cell tumors

immune system

pancreas inflammation ( J:67128 )

• some mice exhibit duct inflammation in the pancreas

digestive/alimentary system

abnormal pancreatic acinar cell morphology ( J:67128 )

• some mice exhibit duct inflammation, acinar cysts, focal acinar dysplasia, and focal acinar necrosis unlike wild-type mice

increased stomach tumor incidence ( J:67128 )

• one mouse developed a gastric neuroendocrine tumor

respiratory system

increased lung adenocarcinoma incidence ( J:67128 )

• in 22% of mice

nervous system

increased pituitary adenoma incidence ( J:67128 )

• pituitary adenomas develop in 26% of mice by 16 months of age

• all pituitary tumors secrete prolactin but not ACTH

increased prolactinoma incidence ( J:67128 )

growth/size/body

thyroid gland cyst ( J:67128 )

• thyroid cysts

pancreas cyst ( J:67128 )

• acinar cysts in some mice

Genotype
MGI:3843203

cn3

• Allelic Composition: Men1^tm1Ctre/Men1^tm1Ctre; Tg(Pdx1-cre)89.1Dam/0
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * CBA * FVB/N

mortality/aging

premature death ( J:146440 )

• 50% of mice are dead by 14 months of age unlike wild-type mice

endocrine/exocrine glands

abnormal pancreatic islet morphology ( J:146440 )

• at 3 and 12 months, the vasculature of some islets is abnormal with dilation of blood vessels and intense tortuosity unlike in wild-type mice

• however, treatment with sunitinib decreases in islet vascularity

enlarged pancreatic islets ( J:146440 )

• as early as 5 to 6 months

pancreatic islet hyperplasia ( J:146440 )

• as early as 5 to 6 months

increased insulinoma incidence ( J:146440 )

• by 10 to 12 months of age, mice develop insulinoma that are filled with blood islands or lacunae unlike wild-type mice

• however, mice do not develop gastrinoma unlike in other MEN1 models

abnormal pancreas physiology ( J:146440 )

• mice exhibit more proliferating cells within their islets compared with wild-type mice

• however, proliferation of exocrine cells is normal and treatment with sunitinib decreases islet cell proliferation

homeostasis/metabolism

decreased circulating glucose level ( J:146440 )

• at 10 months of age

increased circulating insulin level ( J:146440 )

• starting at 5 months of age

neoplasm

increased insulinoma incidence ( J:146440 )

• by 10 to 12 months of age, mice develop insulinoma that are filled with blood islands or lacunae unlike wild-type mice

• however, mice do not develop gastrinoma unlike in other MEN1 models

cardiovascular system

abnormal blood vessel morphology ( J:146440 )

• at 3 and 12 months, the vasculature of some islets is abnormal with dilation of blood vessels and intense tortuosity unlike in wild-type mice

• however, treatment with sunitinib decreases in islet vascularity

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
multiple endocrine neoplasia type 1		DOID:10017	OMIM:131100	J:146440

Genotype
MGI:3843204

cn4

• Allelic Composition: Men1^tm1Ctre/Men1⁺; Tg(Pdx1-cre)89.1Dam/0
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * CBA * FVB/N

homeostasis/metabolism

increased circulating insulin level ( J:146440 )

• at 16 months of age