Phenotypes associated with this allele

• Allele Symbol: Manf^{tm1a(KOMP)Wtsi}
• Allele Name: targeted mutation 1a, Wellcome Trust Sanger Institute
• Allele ID: MGI:4362648
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Manf^tm1a(KOMP)Wtsi/Manf^tm1a(KOMP)Wtsi	involves: C57BL/6 * C57BL/6N * ICR	MGI:6157759
hm2	Manf^tm1a(KOMP)Wtsi/Manf^tm1a(KOMP)Wtsi	involves: C57BL/6N	MGI:6157362

Genotype
MGI:6157759

hm1

• Allelic Composition: Manf^{tm1a(KOMP)Wtsi}/Manf^{tm1a(KOMP)Wtsi}
• Genetic Background: involves: C57BL/6 * C57BL/6N * ICR
• Cell Lines: EPD0162_3_D06

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

endocrine/exocrine glands

increased pancreas apoptosis ( J:211812 )

• increased apoptosis of beta cells at age P14

abnormal pancreatic beta cell differentiation ( J:211812 )

• decreased number of proliferating insulin+ cells at age P1 and P14

• number of proliferating insulin+ cells at embryonic age E18.5

decreased pancreatic beta cell mass ( J:211812 )

• 50% reduction at age P1 and 85% at age P56

• at embryonic age E18.5

decreased pancreatic beta cell number ( J:211812 )

• proliferating insulin+ cells at age P1 and P14

• at age P35

• proliferating insulin+ cells at embryonic age E18.5

decreased pancreatic islet number ( J:211812 )

• at age P35

homeostasis/metabolism

abnormal translation ( J:211812 )

• increased activation of unfolded protein response (UPR) pathway in E18.5 pancreas and cultured isolated islets from P14 pancreas

abnormal glucose homeostasis ( J:211812 )

• at age P1 and P14

• at P56

• insulin sensitivity

• dramatically decreased circulating glucose-stimulated insulin levels at age P56

hyperglycemia ( J:211812 )

• at age P1 and P14

• at P56

decreased circulating insulin level ( J:211812 )

• severely reduced at age P28, barely detectable at age P56

cellular

increased pancreas apoptosis ( J:211812 )

• increased apoptosis of beta cells at age P14

abnormal pancreatic beta cell differentiation ( J:211812 )

• decreased number of proliferating insulin+ cells at age P1 and P14

• number of proliferating insulin+ cells at embryonic age E18.5

abnormal translation ( J:211812 )

• increased activation of unfolded protein response (UPR) pathway in E18.5 pancreas and cultured isolated islets from P14 pancreas

growth/size/body

decreased body size ( J:211812 )

• body weight and size of newborn mice significantly reduced, never attaining wild-type weight or size at age P56

postnatal growth retardation ( J:211812 )

• body weight and size of newborn mice significantly reduced, never attaining wild-type weight or size at age P56

slow postnatal weight gain ( J:211812 )

• body weight of newborn mice significantly lower, never attaining wild-type weight at age P56

fetal growth retardation ( J:211812 )

• embryo weight significantly lower at E18.5

adipose tissue

abnormal fat pad morphology ( J:211812 )

• weight of epididymal fat pads reduced by around 90%

behavior/neurological

polydipsia ( J:211812 )

• significantly increased water consumption at age P56

Genotype
MGI:6157362

hm2

• Allelic Composition: Manf^{tm1a(KOMP)Wtsi}/Manf^{tm1a(KOMP)Wtsi}
• Genetic Background: involves: C57BL/6N

nervous system

nervous system phenotype ( J:255942 )

N • neuronal stem cell (NSC) viability, self-renewal and proliferation with E13.5 embryo NSCs cultured in vitro

N • cell proliferation and apoptosis in E13.5, E15.5 and P1 brains

N • number of neuroepithelial and intermediate progenitor cells in ventricular and subventricular zones in E15.5 brain

N • number of cortical neurons and glial cells in E19 and P7 brains

N • brain weight to body weight ratio

abnormal neuronal migration ( J:255942 )

• fewer Tbr1+ and more Bcl11b (CTIP2)+ neurons in lower layer of E18.5 embryonic cortex

• partially intermingled (instead of in separate layers as in wild-type) Tbr1+ and Bcl11b (CTIP2)+ neurons in E18.5 cortical plate

• fewer BrdU+ cells in cortical plate (CP) and subplate (SP) in E17 embryonic cortex when injected with BrdU at E13.5

• more BrdU+ cells in ventricular (SV) and subventricular (SVZ) zones in E17 embryonic cortex when injected with BrdU at E13.5

• more BrdU+ cells in cortical layers IV and V/VI in E19 embryonic cortex when injected with BrdU at E15.5

abnormal cortical intermediate zone morphology ( J:255942 )

• thinner at E15.5

• higher cell density at E18.5

• thickness at E18.5

abnormal cortical plate morphology ( J:255942 )

• thinner at E15.5 and E18.5

• higher cell density at E18.5

thin cortical plate ( J:255942 )

• at E15.5 and E18.5

increased cerebral cortex cell density ( J:255942 )

• in layers II-IV at age P7

thin cerebral cortex ( J:255942 )

• layers II-IV and V thinner at age P1 and P7

• layer VI thickness

abnormal neuronal stem cell morphology ( J:255942 )

• lack of neurite outgrowth at DIV2 stage in vitro

• decreased neurite length at DIV4 stage in vitro

• fewer Tubb3 (Tuj1)+ and Map2+ differentiated cells at DIV8 stage in vitro

• decreased neurite length in Tubb3 (Tuj1)+ differentiated cells at DIV8 stage in vitro

• number of Gfap+ and Dcx+ cells at DIV8 stage in vitro

• neuronal stem cell (NSC) viability, self-renewal and proliferation with E13.5 embryo NSCs cultured in vitro

• ratio of nestin+ neuronal stem cells (NSCs) and Dcx+ neuronal precursor cells (NPCs) with E13.5 embryo NSCs cultured in vitro

abnormal neurite morphology ( J:255942 )

• shorter Map2+ dendrite extensions in cortex at age P7

• weaker Nefh (NF200) staining of cortical axons at age P7

cellular

abnormal neuronal migration ( J:255942 )

• fewer Tbr1+ and more Bcl11b (CTIP2)+ neurons in lower layer of E18.5 embryonic cortex

• partially intermingled (instead of in separate layers as in wild-type) Tbr1+ and Bcl11b (CTIP2)+ neurons in E18.5 cortical plate

• fewer BrdU+ cells in cortical plate (CP) and subplate (SP) in E17 embryonic cortex when injected with BrdU at E13.5

• more BrdU+ cells in ventricular (SV) and subventricular (SVZ) zones in E17 embryonic cortex when injected with BrdU at E13.5

• more BrdU+ cells in cortical layers IV and V/VI in E19 embryonic cortex when injected with BrdU at E15.5

abnormal translation ( J:255942 )

• lower de novo protein synthesis, as indicated by less homopropargylglycine (HPG)-derived signal level, in neuronal stem cells (NSCs) at DIV2 stage in vitro

• de novo protein synthesis, as indicated by less homopropargylglycine (HPG)-derived signal level, restricted to the soma in neuronal stem cells (NSCs) at DIV2 stage in vitro, compared to soma and growing neurites in wild-type

• increased activation of unfolded protein response (UPR) pathway in neuronal stem cells (NSCs) at DIV1, DIV4 and DIV8 stage in vitro

homeostasis/metabolism

abnormal translation ( J:255942 )

• lower de novo protein synthesis, as indicated by less homopropargylglycine (HPG)-derived signal level, in neuronal stem cells (NSCs) at DIV2 stage in vitro

• de novo protein synthesis, as indicated by less homopropargylglycine (HPG)-derived signal level, restricted to the soma in neuronal stem cells (NSCs) at DIV2 stage in vitro, compared to soma and growing neurites in wild-type

• increased activation of unfolded protein response (UPR) pathway in neuronal stem cells (NSCs) at DIV1, DIV4 and DIV8 stage in vitro