Phenotypes associated with this allele

• Allele Symbol: Men1^tm1Zqw
• Allele Name: targeted mutation 1, Zhao-Qi Wang
• Allele ID: MGI:2664869
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Men1^tm1Zqw/Men1^tm1Zqw	either: (involves: 129/Sv * 129P2/OlaHsd) or (involves: 129P2/OlaHsd * C57BL/6)	MGI:3590309
ht2	Men1^tm1Zqw/Men1^+	involves: 129/Sv * 129P2/OlaHsd	MGI:5009321

Genotype
MGI:3590309

hm1

• Allelic Composition: Men1^tm1Zqw/Men1^tm1Zqw
• Genetic Background: either: (involves: 129/Sv * 129P2/OlaHsd) or (involves: 129P2/OlaHsd * C57BL/6)

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

mortality/aging

lethality throughout fetal growth and development, complete penetrance ( J:83882 )

• embryos begin to die between E12.5 and E13.5

• no homozygotes survive to E15.5

growth/size/body

decreased embryo size ( J:83882 )

• embryos at E11.5-E12.5 were generally smaller in size than wild-type embryos

embryo

decreased embryo size ( J:83882 )

• embryos at E11.5-E12.5 were generally smaller in size than wild-type embryos

abnormal embryonic tissue morphology ( J:83882 )

• abnormal development of the organ systems including the heart and liver as well as neural tube development

abnormal neural tube closure ( J:83882 )

• abnormal neural tube closure showing a zig-zag pattern and rarely exencephaly

• incomplete closure of the dorsal neural tube amd mild envagination of the overlying ectoderm

cardiovascular system

trabecula carnea hypoplasia ( J:83882 )

• clear myocardial hypotrophy in most embryos resulting in decreased thickness and density of ventricular trabeculations

thin interventricular septum ( J:83882 )

• thinner intraventricular septum

thin ventricular wall ( J:83882 )

hemorrhage ( J:83882 )

• body hemorrhages or edemas often found between E11.5 and E12.5

nervous system

abnormal neural tube closure ( J:83882 )

• abnormal neural tube closure showing a zig-zag pattern and rarely exencephaly

• incomplete closure of the dorsal neural tube amd mild envagination of the overlying ectoderm

exencephaly ( J:83882 )

• variable penetrance; severe with open and protruding neuro-ectodermal structures of the forebrain and midbrain

liver/biliary system

delayed hepatic development ( J:83882 )

• severe growth retardation in about 42% of embryos

• abnormal organization of the epithelial and hematopoietic compartments with loosened intercellular contacts and nuclear condensation of hematopoietic and epithelial cells

• many apoptotic cells

muscle

trabecula carnea hypoplasia ( J:83882 )

• clear myocardial hypotrophy in most embryos resulting in decreased thickness and density of ventricular trabeculations

Genotype
MGI:5009321

ht2

• Allelic Composition: Men1^tm1Zqw/Men1⁺
• Genetic Background: involves: 129/Sv * 129P2/OlaHsd

neoplasm

increased gastrointestinal tumor incidence ( J:85302 )

• gastrointestinal lesions were seen in 8/49 heterozygous mice, mainly situated in the duodenum or at the junction of the glandular stomach and duodenum

• histological examination of gastrointestinal lesions revealed adenomas and carcinomas in the duodenum

increased intestinal adenoma incidence ( J:85302 )

• histological examination of gastrointestinal lesions revealed adenomas in the duodenum

• gastrinomas in the duodenum

increased stomach tumor incidence ( J:85302 )

• histological examination of gastrointestinal lesions revealed adenomas and carcinomas in the glandular stomach

• tumors located in the mucosa of the bodyfunds glandular stomach were composed of uniform cells with scanty cytoplasma and invaded the submucosa layer

• gastrinomas in the glandular stomach

increased gland tumor incidence ( J:85302 )

• in heterozygous mice older than 13 months of age, a high incidence of multiple endocrine tumors was noted, and nearly all mice developed more than one endocrine tumor

increased mammary gland tumor incidence ( J:85302 )

• 3/36 heterozygous female mice over 18 months of age exhibited mammary gland carcinomas

increased adrenal gland tumor incidence ( J:85302 )

• histological analysis of 23 glands in homozygous mice showed nodular hyperplasia in two (9%) at 8-12 months of age

• at 13-18 months of age, 7/31 (23%) homozygous mice exhibited nodular hyperplasia

increased adrenal cortical tumor incidence ( J:85302 )

• after 18 months, 28/61 (46%) heterozygous mice developed adenomas or carcinomas in the adrenal cortex

increased adrenal gland adenoma incidence ( J:85302 )

• histological analysis of 23 glands in homozygous mice showed adenomas in three (13%) at 8-12 months of age

• at 13-18 months of age, 4/31 (13%) heterozygous mice developed adrenal adenomas

increased adrenocortical adenoma incidence ( J:85302 )

• after 18 months, heterozygous mice developed adenomas in the adrenal cortex

increased pancreas tumor incidence ( J:85302 )

• islet hyperplasia is seen by eight months of age

• at 8-12 months of age, 15 of 23 (65%) mice contained hyperplastic or dysplastic islets

• in 4/12 islet tumors analyzed, two hormones were expresssed simultaneously, such as insulin and glucagon, or glucagon and gastrin, suggesting a mixed hormone production

increased pancreatic islet cell adenoma incidence ( J:85302 )

• at 8-12 months of age, 5/23 (22%) developed islet adenomas

increased glucagonoma incidence ( J:85302 )

• islet tumors in 6/12 mice showed strong glucagon immunoreactivity, showing alpha-cell tumors or glucagonomas

increased insulinoma incidence ( J:85302 )

• the majority of the islet tumors expressed high levels of insulin and were thus identified as beta-cell insulinomas

increased pancreatic islet cell carcinoma incidence ( J:85302 )

• at 8-12 months of age, 2/23 developed (9%) carcinomas

• 13/34 mice develop islet carcinomas at 13-18 months of age

increased parathyroid adenoma incidence ( J:85302 )

• adenomas are first seen at 12 months of age and were detected in 7/17 (41%) heterozygous mice in the 13- to 18-month age group and 21/33 (64%) mice over 19 months

increased pituitary adenohypophysis tumor incidence ( J:85302 )

• pituitary tumors occur after the age of 18 months and are more common in females (79%)

• 6/15 pituitary tumors showed strong GH immunoreactivity

• however, all pituitary tumors were negative for ACTH staining

increased prolactinoma incidence ( J:85302 )

• 9/15 pituitary tumors showed strong exclusive PRL immunoreactivity

increased thyroid tumor incidence ( J:85302 )

• seen in 4/61 heterozygous mice

increased thyroid carcinoma incidence ( J:85302 )

• thyroid follicular cell hyperplasia localized focally, and solid follicular cell carcinomas contained tumor cells in densely packed nest and forming a few minute follicles

increased gonad tumor incidence ( J:85302 )

• heterozygous mutant mice developed a high frequency of tumors in the gonad

• 9/12 (75%) male heterozygous mice at 8-12 months of age exhibited gonadal stromal hyperplasia or dysplasia and 3/12 (25%) exhibited stromal cell tumors, with the tumor incidence reaching 59% and 88% in the 13- to 18-month and 19- to 26-month age groups,espectively

increased ovary tumor incidence ( J:85302 )

♀ • 19/44 (43%) of heterozygous females developed ovarian tumors between the ages of 13 and 26 months

♀ • histological analysis of these tumors revealed that all were derived from sex-cord stromal cells, mainly granulosa cells, contained large round nuclei; the follicular structure was largely replaced by the tumor mass, and tumor cells expressed high levels of 3beta-HSD, indicating steroidogenesis in the tumor cells

increased testis tumor incidence ( J:85302 )

♂ • the focal stromal hyperplasia and multinodular tumors were seen and were frequently bilateral, compressed the surrounding seminiferous tubules, resulting in degenerative changes

♂ • testis tumor cells were large and often polygonal, with an abundant granular eosinophilic cytoplasm and a central round nucleus, and occasionally contained lipid pigment and vacuoles

increased Leydig cell tumor incidence ( J:85302 )

♂ • testes of heterozygous mice contained hyperplastic stromal cells and tumors, both with strong 3beta-HSD expression, a marker for Leydig cells

endocrine/exocrine glands

enlarged adrenal glands ( J:85302 )

• an enlargement of adrenal glands, often bilateral, is observed in heterozygous mice

enlarged pituitary gland ( J:85302 )

• enlarged pituitary was often found in heterozygous mice beyond 13 months of age

thyroid gland hyperplasia ( J:85302 )

• seen in 4/61 heterozygous mice

enlarged ovary ( J:85302 )

♀ • a marked increase in ovarian size in heterozygous mice after 13 months of age

enlarged testis ( J:85302 )

♂ • a marked increase in ovarian size in heterozygous mice after 13 months of age

increased gland tumor incidence ( J:85302 )

• in heterozygous mice older than 13 months of age, a high incidence of multiple endocrine tumors was noted, and nearly all mice developed more than one endocrine tumor

increased mammary gland tumor incidence ( J:85302 )

• 3/36 heterozygous female mice over 18 months of age exhibited mammary gland carcinomas

increased adrenal gland tumor incidence ( J:85302 )

• histological analysis of 23 glands in homozygous mice showed nodular hyperplasia in two (9%) at 8-12 months of age

• at 13-18 months of age, 7/31 (23%) homozygous mice exhibited nodular hyperplasia

increased adrenal cortical tumor incidence ( J:85302 )

• after 18 months, 28/61 (46%) heterozygous mice developed adenomas or carcinomas in the adrenal cortex

increased adrenal gland adenoma incidence ( J:85302 )

• histological analysis of 23 glands in homozygous mice showed adenomas in three (13%) at 8-12 months of age

• at 13-18 months of age, 4/31 (13%) heterozygous mice developed adrenal adenomas

increased adrenocortical adenoma incidence ( J:85302 )

• after 18 months, heterozygous mice developed adenomas in the adrenal cortex

increased ovary tumor incidence ( J:85302 )

♀ • 19/44 (43%) of heterozygous females developed ovarian tumors between the ages of 13 and 26 months

♀ • histological analysis of these tumors revealed that all were derived from sex-cord stromal cells, mainly granulosa cells, contained large round nuclei; the follicular structure was largely replaced by the tumor mass, and tumor cells expressed high levels of 3beta-HSD, indicating steroidogenesis in the tumor cells

increased pancreas tumor incidence ( J:85302 )

• islet hyperplasia is seen by eight months of age

• at 8-12 months of age, 15 of 23 (65%) mice contained hyperplastic or dysplastic islets

• in 4/12 islet tumors analyzed, two hormones were expresssed simultaneously, such as insulin and glucagon, or glucagon and gastrin, suggesting a mixed hormone production

increased pancreatic islet cell adenoma incidence ( J:85302 )

• at 8-12 months of age, 5/23 (22%) developed islet adenomas

increased glucagonoma incidence ( J:85302 )

• islet tumors in 6/12 mice showed strong glucagon immunoreactivity, showing alpha-cell tumors or glucagonomas

increased insulinoma incidence ( J:85302 )

• the majority of the islet tumors expressed high levels of insulin and were thus identified as beta-cell insulinomas

increased pancreatic islet cell carcinoma incidence ( J:85302 )

• at 8-12 months of age, 2/23 developed (9%) carcinomas

• 13/34 mice develop islet carcinomas at 13-18 months of age

increased parathyroid adenoma incidence ( J:85302 )

• adenomas are first seen at 12 months of age and were detected in 7/17 (41%) heterozygous mice in the 13- to 18-month age group and 21/33 (64%) mice over 19 months

increased pituitary adenohypophysis tumor incidence ( J:85302 )

• pituitary tumors occur after the age of 18 months and are more common in females (79%)

• 6/15 pituitary tumors showed strong GH immunoreactivity

• however, all pituitary tumors were negative for ACTH staining

increased prolactinoma incidence ( J:85302 )

• 9/15 pituitary tumors showed strong exclusive PRL immunoreactivity

increased testis tumor incidence ( J:85302 )

♂ • the focal stromal hyperplasia and multinodular tumors were seen and were frequently bilateral, compressed the surrounding seminiferous tubules, resulting in degenerative changes

♂ • testis tumor cells were large and often polygonal, with an abundant granular eosinophilic cytoplasm and a central round nucleus, and occasionally contained lipid pigment and vacuoles

increased Leydig cell tumor incidence ( J:85302 )

♂ • testes of heterozygous mice contained hyperplastic stromal cells and tumors, both with strong 3beta-HSD expression, a marker for Leydig cells

increased thyroid tumor incidence ( J:85302 )

• seen in 4/61 heterozygous mice

increased thyroid carcinoma incidence ( J:85302 )

• thyroid follicular cell hyperplasia localized focally, and solid follicular cell carcinomas contained tumor cells in densely packed nest and forming a few minute follicles

nervous system

enlarged pituitary gland ( J:85302 )

• enlarged pituitary was often found in heterozygous mice beyond 13 months of age

increased pituitary adenohypophysis tumor incidence ( J:85302 )

• pituitary tumors occur after the age of 18 months and are more common in females (79%)

• 6/15 pituitary tumors showed strong GH immunoreactivity

• however, all pituitary tumors were negative for ACTH staining

increased prolactinoma incidence ( J:85302 )

• 9/15 pituitary tumors showed strong exclusive PRL immunoreactivity

reproductive system

enlarged ovary ( J:85302 )

♀ • a marked increase in ovarian size in heterozygous mice after 13 months of age

enlarged testis ( J:85302 )

♂ • a marked increase in ovarian size in heterozygous mice after 13 months of age

increased gonad tumor incidence ( J:85302 )

• heterozygous mutant mice developed a high frequency of tumors in the gonad

• 9/12 (75%) male heterozygous mice at 8-12 months of age exhibited gonadal stromal hyperplasia or dysplasia and 3/12 (25%) exhibited stromal cell tumors, with the tumor incidence reaching 59% and 88% in the 13- to 18-month and 19- to 26-month age groups,espectively

increased ovary tumor incidence ( J:85302 )

♀ • 19/44 (43%) of heterozygous females developed ovarian tumors between the ages of 13 and 26 months

♀ • histological analysis of these tumors revealed that all were derived from sex-cord stromal cells, mainly granulosa cells, contained large round nuclei; the follicular structure was largely replaced by the tumor mass, and tumor cells expressed high levels of 3beta-HSD, indicating steroidogenesis in the tumor cells

increased testis tumor incidence ( J:85302 )

♂ • the focal stromal hyperplasia and multinodular tumors were seen and were frequently bilateral, compressed the surrounding seminiferous tubules, resulting in degenerative changes

♂ • testis tumor cells were large and often polygonal, with an abundant granular eosinophilic cytoplasm and a central round nucleus, and occasionally contained lipid pigment and vacuoles

increased Leydig cell tumor incidence ( J:85302 )

♂ • testes of heterozygous mice contained hyperplastic stromal cells and tumors, both with strong 3beta-HSD expression, a marker for Leydig cells

digestive/alimentary system

increased gastrointestinal tumor incidence ( J:85302 )

• gastrointestinal lesions were seen in 8/49 heterozygous mice, mainly situated in the duodenum or at the junction of the glandular stomach and duodenum

• histological examination of gastrointestinal lesions revealed adenomas and carcinomas in the duodenum

increased intestinal adenoma incidence ( J:85302 )

• histological examination of gastrointestinal lesions revealed adenomas in the duodenum

• gastrinomas in the duodenum

increased stomach tumor incidence ( J:85302 )

• histological examination of gastrointestinal lesions revealed adenomas and carcinomas in the glandular stomach

• tumors located in the mucosa of the bodyfunds glandular stomach were composed of uniform cells with scanty cytoplasma and invaded the submucosa layer

• gastrinomas in the glandular stomach

growth/size/body

enlarged ovary ( J:85302 )

♀ • a marked increase in ovarian size in heterozygous mice after 13 months of age

integument

increased mammary gland tumor incidence ( J:85302 )

• 3/36 heterozygous female mice over 18 months of age exhibited mammary gland carcinomas

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
growth hormone secreting pituitary adenoma		DOID:6255		J:85302
hyperparathyroidism		DOID:13543	OMIM:145000 OMIM:145001 OMIM:610071	J:85302
multiple endocrine neoplasia type 1		DOID:10017	OMIM:131100	J:85302
prolactinoma		DOID:5394		J:85302