Phenotypes associated with this allele

• Allele Symbol: Insm1^tm1Cbm
• Allele Name: targeted mutation 1, Carmen Birchmeier
• Allele ID: MGI:3656035
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Insm1^tm1Cbm/Insm1^tm1Cbm	involves: 129P2/OlaHsd	MGI:5573165
hm2	Insm1^tm1Cbm/Insm1^tm1Cbm	involves: 129P2/OlaHsd * C57BL/6	MGI:3662846
hm3	Insm1^tm1Cbm/Insm1^tm1Cbm	involves: 129P2/OlaHsd * C57BL/6 * CD-1	MGI:3662845
ht4	Insm1^tm1Cbm/Insm1^tm2.1Cbm	involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ	MGI:5573164

Genotype
MGI:5573165

hm1

• Allelic Composition: Insm1^tm1Cbm/Insm1^tm1Cbm
• Genetic Background: involves: 129P2/OlaHsd

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

homeostasis/metabolism

decreased pituitary hormone level ( J:206319 )

• decreased melanocyte-stimulating hormone, prolactin and adrenocorticotropin levels

• absent growth hormone, follicle stimulating hormone, thyroid-stimulating hormone and luteinizing hormone levels

decreased adrenocorticotropin level ( J:206319 )

decreased follicle stimulating hormone level ( J:206319 )

• absent

decreased growth hormone level ( J:206319 )

• absent at E17.5

decreased luteinizing hormone level ( J:206319 )

• absent

decreased prolactin level ( J:206319 )

decreased thyroid-stimulating hormone level ( J:206319 )

• absent

nervous system

absent somatotrophs ( J:206319 )

• as determined by the lack of growth hormone at E17.5

absent thyrotrophs ( J:206319 )

abnormal pituitary gland development ( J:206319 )

• mice exhibit an increase in endocrine progenitor cells compared with wild-type mice

• however, mice exhibit normal distribution and morphology of fibroblasts, folliculostellate cells and endothelia

small pituitary gland ( J:206319 )

• mild

endocrine/exocrine glands

absent somatotrophs ( J:206319 )

• as determined by the lack of growth hormone at E17.5

absent thyrotrophs ( J:206319 )

abnormal pituitary gland development ( J:206319 )

• mice exhibit an increase in endocrine progenitor cells compared with wild-type mice

• however, mice exhibit normal distribution and morphology of fibroblasts, folliculostellate cells and endothelia

small pituitary gland ( J:206319 )

• mild

Genotype
MGI:3662846

hm2

• Allelic Composition: Insm1^tm1Cbm/Insm1^tm1Cbm
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

mortality/aging

neonatal lethality, complete penetrance ( J:112173 )

• all remaining homozygotes die shortly after birth

perinatal lethality, incomplete penetrance ( J:112173 )

• Background Sensitivity: lethality is increased compared to mice on a mixed 129P2/OlaHsd, C57BL/6, and CD-1 background

• at E18.5 only 4 of 76 mice (5.2%) were homozygous

respiratory system

respiratory failure ( J:112173 )

homeostasis/metabolism

cyanosis ( J:112173 )

endocrine/exocrine glands

decreased pancreatic beta cell number ( J:112173 )

• beta cell, but not alpha cell, numbers are decreased

Genotype
MGI:3662845

hm3

• Allelic Composition: Insm1^tm1Cbm/Insm1^tm1Cbm
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * CD-1

mortality/aging

neonatal lethality, complete penetrance ( J:112173 )

• all remaining homozygotes die shortly after birth

perinatal lethality, incomplete penetrance ( J:112173 )

• Background Sensitivity: lethality is decreased compared to mice on a mixed 129P2/OlaHsd and C57BL/6 background

• at E18.5 only 60 of 451 mice (13%) were homozygous

respiratory system

respiratory failure ( J:112173 )

homeostasis/metabolism

cyanosis ( J:112173 )

digestive/alimentary system

abnormal enteroendocrine cell morphology ( J:112173 )

• while the overall number of lacZ expressing cells is similar to wild-type the number of entero-endocrine cells expressing chromogranin A, cholecystokinin, peptide YY, or serotonin is severely reduced and synaptophysin, neurotensisn, and substance P expressing cells are absent suggesting a block in differentiation of these cells

• however, the proportion of cell expressing secretin is similar to controls

endocrine/exocrine glands

increased pancreas apoptosis ( J:112173 )

• increase in the number of apoptotic cells at E18.5

absent PP cells ( J:112173 )

• at E18.5 many cells are present that do not express any pancreatic hormone unlike in controls

increased PP cell number ( J:112173 )

• the proportion of cells expressing pancreatic polypeptide is increased

decreased pancreatic alpha cell number ( J:112173 )

• numbers of glucagon+ cells are reduced at E12.5 and E15.5; however by E18.5 the proportion of cells is similar to controls

decreased pancreatic beta cell number ( J:112173 )

• numbers of insulin+ cells are similar to wild-type at E12.5 but significantly decreased but E15.5

• at E18.5 a 92% reduction in the number of beta cells is seen

decreased pancreatic delta cell number ( J:112173 )

• at E18.5 the proportion of somatostatin+ cells is decreased

decreased pancreatic epsilon cell number ( J:112173 )

• the proportion of cells expressing ghrelin is decreased

pancreatic islet hypoplasia ( J:112173 )

• increased density of nuclei and 26% reduction in the overall endocrine cell numbers

abnormal endocrine pancreas development ( J:112173 )

• development of the endocrine but not the exocrine pancreas is impaired

cellular

increased pancreas apoptosis ( J:112173 )

• increase in the number of apoptotic cells at E18.5

Genotype
MGI:5573164

ht4

• Allelic Composition: Insm1^tm1Cbm/Insm1^tm2.1Cbm
• Genetic Background: involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ

homeostasis/metabolism

decreased pituitary hormone level ( J:206319 )

• decreased melanocyte-stimulating hormone, prolactin and adrenocorticotropin levels

• absent growth hormone, follicle stimulating hormone, thyroid-stimulating hormone and luteinizing hormone levels

decreased adrenocorticotropin level ( J:206319 )

decreased follicle stimulating hormone level ( J:206319 )

• absent

decreased growth hormone level ( J:206319 )

• absent

decreased luteinizing hormone level ( J:206319 )

• absent

decreased prolactin level ( J:206319 )

decreased thyroid-stimulating hormone level ( J:206319 )

• absent