Mouse Genome Informatics
hm1
    Nf1tm1Tyj/Nf1tm1Tyj
involves: 129S2/SvPas
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• a higher percentage of cells behave as neural crest stem cells (form multipotent neurospheres) in cultures made from the sympathetic chain, dorsal root ganglia, and sciatic nerve, but not the gut, of E13 homozygous embryos compared to littermate controls
• neurospheres are larger, proliferation is increased, and the capacity for self-renewal is increased in cultured neural crest stem cells from the sympathetic chain, dorsal root ganglia, and sciatic nerve of E13 homozygous embryos compared to littermate controls
• when stimulated to differentiate these neural crest stem cells produce more glia without any decrease in any of the other cell types (neurons, myofibroblasts) produced
• survival of these neural crest stem cells is improved under adverse culture conditions compared to cells from littermate controls

embryogenesis
• a higher percentage of cells behave as neural crest stem cells (form multipotent neurospheres) in cultures made from the sympathetic chain, dorsal root ganglia, and sciatic nerve, but not the gut, of E13 homozygous embryos compared to littermate controls
• neurospheres are larger, proliferation is increased, and the capacity for self-renewal is increased in cultured neural crest stem cells from the sympathetic chain, dorsal root ganglia, and sciatic nerve of E13 homozygous embryos compared to littermate controls
• when stimulated to differentiate these neural crest stem cells produce more glia without any decrease in any of the other cell types (neurons, myofibroblasts) produced
• survival of these neural crest stem cells is improved under adverse culture conditions compared to cells from littermate controls


Mouse Genome Informatics
hm2
    Nf1tm1Tyj/Nf1tm1Tyj
involves: 129S2/SvPas * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging

cardiovascular system
• myocardium, particularly of the ventricles, was lacy in appearance and thinner than normal

homeostasis/metabolism
• begin to exhibit edema at E12.5

integument


Mouse Genome Informatics
ht3
    Nf1tm1Tyj/Nf1+
involves: 129S2/SvPas
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• bone marrow derived mast cells have about a 25% faster proliferation rate than controls when cultured for three days with SCF
• these mast cells also have a two-thirds higher migration rate towards SCF in transwell assays than controls
• a similar higher migration rate to the skin is observed in vivo when SCF is administered
• the percent of degranulating mast cells in SCF-treated skin is almost 4 times that of controls

hematopoietic system
• bone marrow derived mast cells have about a 25% faster proliferation rate than controls when cultured for three days with SCF
• these mast cells also have a two-thirds higher migration rate towards SCF in transwell assays than controls
• a similar higher migration rate to the skin is observed in vivo when SCF is administered
• the percent of degranulating mast cells in SCF-treated skin is almost 4 times that of controls


Mouse Genome Informatics
ht4
    Nf1tm1Tyj/Nf1+
involves: 129S2/SvPas * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• 75% of mice develop tumors over 27 months, including lymphomas, leukemias, lung adenocarcinomas, hepatomas, fibrosarcomas, neurofibrosarcoma, and adrenal tumors
• mice develop similar types of tumors seen in patients with neurofibromatosis, but do not present any other classical features of the disease
• some heterozygotes developed lymphoid leukemia and myeloid leukemia

Mouse Models of Human Disease
OMIM IDRef(s)
NOT Neurofibromatosis, Type I; NF1 162200 J:18542


Mouse Genome Informatics
ht5
    Nf1tm1Tyj/Nf1+
involves: 129S2/SvPas * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
• impairment in Morris Water Maze that was overcome with extensive training, however normal long term memory in cued fear conditioning test and normal nociception

Mouse Models of Human Disease
OMIM IDRef(s)
Neurofibromatosis, Type I; NF1 162200 J:38703


Mouse Genome Informatics
ht6
    Nf1tm1Tyj/Nf1tm2Tyj
chimera involves: 129S2/SvPas
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• mice exhibiting a high degree of chimerism are all dead by one month of age

muscle
• mice exhibiting a moderate degree of chimerism exhibit muscle dysplasia

normal phenotype
• mice exhibiting a low degree of chimerism exhibit normal pathology

tumorigenesis
• mice exhibiting a moderate degree of chimerism exhibit an increased incidence of neurofibromas; plexiform neurofibromas only, no dermal neurofibromas


Mouse Genome Informatics
cn7
    Nf1tm1Par/Nf1tm1Tyj
Tg(Wnt1-cre)11Rth/0

involves: 129/Sv * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
embryogenesis
• increase in the frequency of neural crest stem cells in the sympathetic chain, dorsal root ganglia, and sciatic nerve at E13 but not at E17 to E19

nervous system
• increase in the frequency of neural crest stem cells in the sympathetic chain, dorsal root ganglia, and sciatic nerve at E13 but not at E17 to E19


Mouse Genome Informatics
cn8
    Nf1tm1Par/Nf1tm1Tyj
Tg(P0-Cre)1Gth/0

involves: 129/Sv * FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
N
• neural crest stem cells do not abnormally persist in the peripheral nervous system in adult mice (J:131914)

tumorigenesis
• at 15 - 20 months of age, all 6 mice examined had plexiform neurofibromas compared to 0 fibromas in control littermates


Mouse Genome Informatics
cn9
    Nf1tm1Par/Nf1tm1Tyj
Tg(Postn-cre)1Sjc/0

involves: 129S1/Sv * 129S2/SvPas * 129X1/SvJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• only 6 of 32 mice survived beyond 4 weeks of age

tumorigenesis
N
• unlike mice crossed to Tg(P0-Cre)1Gth tumors are not seen in surviving adults (J:131914)

embryogenesis
• increase in the frequency of neural crest stem cells in the sympathetic chain and sciatic nerve, but not the gut, at E15 but not in surviving adults

nervous system
• increase in the frequency of neural crest stem cells in the sympathetic chain and sciatic nerve, but not the gut, at E15 but not in surviving adults


Mouse Genome Informatics
cx10
    Nf1tm1Tyj/Nf1+
Trp53tm1Tyj/Trp53+

(C3H/HeJ x B6.129S2-Trp53tm1Tyj Nf1tm1Tyj/+ +)F1
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• in mice with advanced tumors

tumorigenesis
• Background Sensitivity: mice on a congenic C57BL/6 or C3H/HeJ F1 background develop more brain tumors compared with mice on a CAST/EiJ or SJL/J F1 background
• brain tumors range from diffuse cells with nuclear atypia to glioblastoma multiforme

behavior/neurological
• in mice with advanced tumors
• in mice with advanced tumors


Mouse Genome Informatics
cx11
    Nf1tm1Tyj/Nf1+
Trp53tm1Tyj/Trp53+

(CAST/EiJ x B6.129S2-Trp53tm1Tyj Nf1tm1Tyj/+ +)F1
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• in mice with advanced tumors

tumorigenesis
• brain tumors range from diffuse cells with nuclear atypia to glioblastoma multiforme
• Background Sensitivity: mice on a congenic C57BL/6 or C3H/HeJ F1 background develop more brain tumors compared with mice on a CAST/EiJ or SJL/J F1 background

behavior/neurological
• in mice with advanced tumors
• in mice with advanced tumors


Mouse Genome Informatics
cx12
    Nf1tm1Tyj/Nf1+
Trp53tm1Tyj/Trp53+

(CBA/J x B6.129S2-Trp53tm1Tyj Nf1tm1Tyj/+ +)F1
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis


Mouse Genome Informatics
cx13
    Nf1tm1Tyj/Nf1+
Trp53tm1Tyj/Trp53+

(SJL/J x B6.129S2-Trp53tm1Tyj Nf1tm1Tyj/+ +)F1
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• in mice with advanced tumors

tumorigenesis
• brain tumors range from diffuse cells with nuclear atypia to glioblastoma multiforme
• Background Sensitivity: mice on a congenic C57BL/6 or C3H/HeJ F1 background develop more brain tumors compared with mice on a CAST/EiJ or SJL/J F1 background

behavior/neurological
• in mice with advanced tumors
• in mice with advanced tumors


Mouse Genome Informatics
cx14
    Nf1tm1Tyj/Nf1+
Trp53tm1Tyj/Trp53+

B6.129S2-Trp53tm1Tyj Nf1tm1Tyj/+ +
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• in mice with advanced tumors

tumorigenesis
• brain tumors range from diffuse cells with nuclear atypia to glioblastoma multiforme
• Background Sensitivity: mice on a congenic C57BL/6 or C3H/HeJ F1 background develop more brain tumors compared with mice on a CAST/EiJ or SJL/J F1 background

behavior/neurological
• in mice with advanced tumors
• in mice with advanced tumors


Mouse Genome Informatics
cx15
    Nf1tm1Tyj/Nf1tm1Tyj
Rasa1tm1Paw/Rasa1tm1Paw

either: (involves: 129S1/Sv * 129X1/SvJ) or (involves: 129S1/Sv * 129X1/SvJ * C57BL/6) or (involves: 129S1/Sv * 129X1/SvJ * CD-1)
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cardiovascular system
• the heart and surrounding trunk are abnormal

embryogenesis
• cell death is widespread in migrating cranial neural crest
• embryo turning usually failed
• lacking or abnormal
• localized regions of cell proliferation and outgrowth in the neural tube
• fewer than 8 disorganized somites
• arrested development around E8.5

hearing/vestibular/ear
• otic placodes develop but do not develop into vesicles

nervous system
• localized regions of cell proliferation and outgrowth in the neural tube
• midbrain fails to develop
• failure of forebrain structures to develop
• dorsal surface of the hindbrain failed to close
• cell death was widespread in the hindbrain

craniofacial
• lacking or abnormal

limbs/digits/tail

cellular
• cell death is widespread in migrating cranial neural crest


Mouse Genome Informatics
cx16
    Nf1tm1Tyj/Nf1+
Trp53tm1Tyj/Trp53+

involves: 129/Sv * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• cis-double heterozygotes die by 5 months of age and trans-double heterozygotes survive to the average age of 10 months

tumorigenesis
• cis-double heterozygotes exhibit greater incidence of tumors than trans-double heterozygotes
• developed in both cis- and trans-double heterozygotes
• sarcomas in trans-double heterozygotes were similar to those found in mice with either single mutation and were usually correlated with loss of one chromosome
• develop in cis-double heterozygotes, usually correlated with loss of one chromosome

Mouse Models of Human Disease
OMIM IDRef(s)
Neurofibromatosis, Type I; NF1 162200 J:58876


Mouse Genome Informatics
cx17
    Nf1tm1Tyj/Nf1+
Trp53tm1Tyj/Trp53+

involves: 129S2/SvPas
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
N
• neural crest stem cells do not abnormally persist in the peripheral nervous system in adult mice (J:131914)

tumorigenesis
• form by 6 months of age


Mouse Genome Informatics
cx18
    Nf1tm1Tyj/?
Trp53tm1Tyj/?
Mastr129S4/SvJae/?

involves: 129S2/SvPas * 129S4/SvJae * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• astrocytoma resistance


Mouse Genome Informatics
cx19
    Nf1tm1Tyj/?
Trp53tm1Tyj/?
MastrC57BL/6J/?

involves: 129S2/SvPas * 129S4/SvJae * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• astrocytoma susceptibility


Mouse Genome Informatics
cx20
    Cdkn2atm2.1Rdp/Cdkn2atm2.1Rdp
Nf1tm1Tyj/Nf1+

involves: 129S2/SvPas * 129S6/SvEvTac
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
N
• unlike other mice with at least one Nf1 allele, mice do not display malignant peripheral nerve sheath tumors or neurofibromas (J:131914)
• hematopoietic neoplasms, especially lymphoma, are seen in some mice


Mouse Genome Informatics
cx21
    Cdkn2atm1Rdp/Cdkn2atm1Rdp
Nf1tm1Tyj/Nf1+

involves: 129S2/SvPas * 129S6/SvEvTac
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• virtually all mice die by 10 months of age

tumorigenesis
• seen in some mice
• significant frequency of hematopoietic neoplasms consisting mainly of lymphomas and histiocytic neoplasms with lower incidences of acute myeloid leukemias and myeloproliferative disease
• developed in 26% of mice
• in most cases these tumors are grossly evident by 4 to 6 months of age

nervous system
N
• neural crest stem cells do not abnormally persist in the peripheral nervous system in adult mice (J:131914)


Mouse Genome Informatics
cx22
    Cdkn2atm1Rdp/Cdkn2a+
Nf1tm1Tyj/Nf1+

involves: 129S2/SvPas * 129S6/SvEvTac
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• seen at lower frequencies and greater age (over 1 year) compared to mice heterozygous for Nf1 and homozygous for Cdkn2a


Mouse Genome Informatics
cx23
    Nf1tm1Tyj/Nf1+
Trp53tm1Brd/Trp53+

involves: 129S2/SvPas * 129S7/SvEvBrd * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• cis-double heterozygotes died at 15 weeks and trans-double heterozygotes died at 25 weeks

tumorigenesis
• developed in cis-double heterozygotes
• developed in cis-double heterozygotes
• developed in cis-double heterozygotes
• developed in cis-double heterozygotes
• developed in cis-double heterozygotes
• both cis- and trans-double heterozygotes developed sarcomas
• developed in cis-double heterozygotes
• developed in cis-double heterozygotes
• developed in cis-double heterozygotes

integument
• developed in cis-double heterozygotes

Mouse Models of Human Disease
OMIM IDRef(s)
Neurofibromatosis, Type I; NF1 162200 J:58877


Mouse Genome Informatics
cx24
    Nf1tm1Tyj/Nf1+
Trp53tm1Brd/Trp53tm1Brd

involves: 129S2/SvPas * 129S7/SvEvBrd * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• die as early as 3 weeks of age

tumorigenesis
• develop tumors, primarily lymphomas


Mouse Genome Informatics
cx25
    Nf1tm1Tyj/?
Nstr1A/J/?
Trp53tm1Tyj/?

involves: 129S2/SvPas * A/J * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• resistance to peripheral nerve sheath tumors


Mouse Genome Informatics
cx26
    Nf1tm1Tyj/?
Nstr1C57BL/6J/Nstr1C57BL/6J
Trp53tm1Tyj/?

involves: 129S2/SvPas * A/J * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• susceptibility to developing peripheral nerve sheath tumors


Mouse Genome Informatics
cx27
    Nf1tm1Tyj/?
Nstr2A/J/?
Trp53tm1Tyj/?

involves: 129S2/SvPas * A/J * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• resistance to peripheral nerve sheath tumors


Mouse Genome Informatics
cx28
    Nf1tm1Tyj/Nf1+
Tg(Th-MYCN)41Waw/0

involves: 129S2/SvPas * BALB/c * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• mutants exhibit a decreased latency and an increased incidence of tumors compared to single hemizygous Tg(Th-MYCN)41Waw mice, such that about 75% of mutants develop neuroblastomas by 10 months of age compared to 40% of single hemizygous Tg(Th-MYCN)41Waw mice

Mouse Models of Human Disease
OMIM IDRef(s)
Neuroblastoma, Susceptibility to 256700 J:41126


Mouse Genome Informatics
cx29
    Nf1tm1Tyj/Nf1+
Pak1tm1Cher/Pak1tm1Cher

involves: 129S2/SvPas * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• bone marrow derived mast cells proliferate at 60% the rate as controls when cultured for three days with SCF
• migration rates and degranulation of mast cells in response to SCF-treatment is similar to wild-type controls

hematopoietic system
• bone marrow derived mast cells proliferate at 60% the rate as controls when cultured for three days with SCF
• migration rates and degranulation of mast cells in response to SCF-treatment is similar to wild-type controls


Mouse Genome Informatics
cx30
    Grin1tm1Stl/Grin1+
Nf1tm1Tyj/Nf1+

involves: 129S2/SvPas * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
• spatial learning impairment in Morris Water Maze Test, however normal long term memory in cued fear conditioning test and normal nociception

Mouse Models of Human Disease
OMIM IDRef(s)
Neurofibromatosis, Type I; NF1 162200 J:38703