Mouse Genome Informatics
cn1
    Ccm2tm1Etl/Ccm2tm1Etl
Tg(Nes-cre)1Kln/?

B6.Cg-Ccm2tm1Etl Tg(Nes-cre)1Kln
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
normal phenotype

Mouse Models of Human Disease
OMIM IDRef(s)
NOT Cerebral Cavernous Malformations 2; CCM2 603284 J:146210


Mouse Genome Informatics
cn2
    Foxa2tm1.1Stf/Foxa2tm1.1Stf
Tg(Nes-cre)1Kln/0

B6.Cg-Foxa2tm1.1Stf Tg(Nes-cre)1Kln
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
• in fed mice and mice fed a high fat diet
• in fasting mice and mice fed a high fat diet
• in mice fed regular chow or a high fat diet
• glucose clearance is modestly increased compared to in wild-type mice
• indicated by reduced fasting plasma insulin and free fatty acid

behavior/neurological
• in mice fed a high fat diet
• in mice fed regular chow or a high fat diet

adipose tissue
• in mice fed regular chow or a high fat diet

growth/size/body
• in mice fed regular chow or a high fat diet
• in mice fed regular chow or a high fat diet


Mouse Genome Informatics
cn3
    Kalrntm2Npl/Kalrntm2Npl
Tg(Nes-cre)1Kln/0

B6.Cg-Kalrntm2Npl Tg(Nes-cre)1Kln
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
• on a rotarod


Mouse Genome Informatics
cn4
    Mc3rtm1Butl/Mc3rtm1Butl
Tg(Nes-cre)1Kln/0

B6.Cg-Mc3rtm1Butl Tg(Nes-Cre)1Kln
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
growth/size/body
• on a standard chow diet

adipose tissue
• increase in fat mass in mice on a standard diet is attenuated compared to homozygous mice not expressing the cre transgene

homeostasis/metabolism


Mouse Genome Informatics
cn5
    Myd88tm1Jcbr/Myd88tm1Jcbr
Tg(Nes-cre)1Kln/0

B6.Cg-Myd88tm1Jcbr Tg(Nes-cre)1Kln
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
• at 12 weeks, male mice fed a high fat diet exhibit increased energy expenditure during the nighttime compared with similarly treated wild-type mice
• when fed a high fat diet, mice exhibit reduced weight gain and female mice exhibit no weight gain unlike similarly treated wild-type mice
• mice fed a high fat diet exhibit a blunted impairment of glucose and insulin tolerance and insulin serum levels compared with similarly treated wild-type mice
• in male mice fed a high fat diet compared with similarly treated wild-type mice
• when fed a high fat diet, male mice exhibit improved insulin sensitivity compared with similarly treated wild-type mice
• when fed a high fat diet and treated with palmitate, mice exhibit a blunted insulin resistance compared with similarly treated wild-type mice

adipose tissue
• when fed a high fat diet, female mice exhibit a 24% in total fat mass compared with similarly treated wild-type mice
• when fed a high fat diet compared with similarly treated wild-type mice
• slightly in male mice fed a high fat diet compared with similarly treated wild-type mice
• when fed a high fat diet, female mice exhibit a 60% reduction in parametiral fat mass compared with similarly treated wild-type mice

behavior/neurological
• at 12 weeks, male mice fed a high fat diet exhibit reduced food intake compared with similarly treated wild-type mice
• female mice fed a high fat diet and treated with leptin exhibit decreased food intake unlike similarly treated wild-type mice
• male mice fed a high fat diet and treated with leptin exhibit a greater decrease in eating compared with similarly treated wild-type mice
• male mice fed a high fat diet exhibit decreased activity during the nighttime compared with similarly treated wild-type mice

growth/size/body
• when fed a high fat diet, female mice exhibit a 24% in total fat mass compared with similarly treated wild-type mice
• when fed a high fat diet, mice fail to exhibit an increase in length unlike similarly treated wild-type mice
• when fed a high fat diet, mice exhibit reduced weight gain and female mice exhibit no weight gain unlike similarly treated wild-type mice


Mouse Genome Informatics
cn6
    Prmt5tm2c(EUCOMM)Wtsi/Prmt5tm2c(EUCOMM)Wtsi
Tg(Nes-cre)1Kln/0

B6.Cg-Prmt5tm2c(EUCOMM)Wtsi Tg(Nes-cre)1Kln

cell line(s): EPD0160_2_A08
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• all die by P14

nervous system
• apoptotic cells are detected at E15.5 in the ventricular/subventricular zone and ganglionic eminence
• decrease in the number of proliferating neuronal precursor cells at P0
• decrease in the number of primary neurospheres and the number of cells in the neurospheres produced by cultured neuronal precursor cells from E14.5 mice
• self renewal potential of neuronal precursor cells is impaired
• reduced cellularity at P0
• reduced cellularity at P0
• detectable at E17.5
• enlarged and disrupted at P10

behavior/neurological
• balance disorders

cellular
• apoptotic cells are detected at E15.5 in the ventricular/subventricular zone and ganglionic eminence
• decrease in the number of proliferating neuronal precursor cells at P0
• decrease in the number of primary neurospheres and the number of cells in the neurospheres produced by cultured neuronal precursor cells from E14.5 mice
• self renewal potential of neuronal precursor cells is impaired


Mouse Genome Informatics
cn7
    Slc1a2tm1.1Ncd/Slc1a2tm1.1Ncd
Tg(Nes-cre)1Kln/0

B6.Cg-Slc1a2tm1.1Ncd Tg(Nes-cre)1Kln
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• 50% survival after 8 weeks
• higher mortality rate after 3 weeks, with only 50% survival after 8 weeks

growth/size/body

behavior/neurological
• mice become hyperactive after about 2 weeks
• spontaneous seizures are seen after about 2 weeks

nervous system
• spontaneous seizures are seen after about 2 weeks


Mouse Genome Informatics
cn8
    Slc6a12tm1.1Ncd/Slc6a12tm1.1Ncd
Tg(Nes-cre)1Kln/0

B6.Cg-Slc6a12tm1.1Ncd Tg(Nes-cre)1Kln
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
N
• mice exhibit normal seizure threshold (corneal kindling, the minimal clonic and minimal tonic extension seizure threshold tests, the 6 Hz seizure threshold test, and the i.v. pentylenetetrazol threshold test) (J:180428)


Mouse Genome Informatics
cn9
    Ndufs4tm1Rpa/Ndufs4tm1Rpa
Tg(Nes-cre)1Kln/0

B6.Cg-Tg(Nes-cre)1Kln Ndufs4tm1Rpa
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• more than 90% mortality by P50

growth/size/body
• mutants show growth retardation and fail to thrive

respiratory system
• intermittent breathing irregularities, including hypo- or hyperventilation and gasping
• breathing rate is variable and lower in restrained mutants than in controls
• mutants exhibit intermittent episodes of apnea and periods during which respiratory frequency is very irregular; number of apnea episodes increases with age
• gasping-like episodes that occur more commonly under stressful conditions, such as when being handled
• under normoxic conditions, mice at P8-P12 and those older than P30 have normal respiratory frequency, however they have higher tidal volume and minute ventilation
• in response to hypoxia, mutants show an initial augmentation of breathing, followed by a depression
• some mutants exhibit an abnormal response to excess CO2 (hypercapnia), with 6 of 13 mice failing to show the hyperventilation response seen in control mice, while the rest show an exaggerated response

nervous system
• edematous regions/lesions in the dorsal medulla (in the vestibular nucleus)
• extensive bilateral neuroinflammation in the vestibular nucleus
• edematous regions/lesions in the external plexiform layer of the olfactory bulb
• edematous regions/lesions in the cerebellar lobes
• edematous regions/lesions in the deep cerebellar fastigial nucleus
• neurons with cytoplasmic vacuoles are seen in the brain
• progressive gliosis in the brain
• microglial activation is rarely seen in respiratory centers such as the medial parabrachial nucleus, nucleus of the solitary tract or preBotzinger complex, however it is seen in late-stage mutants around serotonergic cell bodies in the medullary raphe
• mutants develop a fatal progressive encephalopathy
• neurons with cytoplasmic vacuoles and aberrant mitochondria containing condensed cristae and microglia engorged with cytoplasmic remnants in the brain
• mutants exhibit abnormal responses of the Botzinger complex in the ventral medulla under hypoxic conditions; the initial augmentation phase is normal but during depression, the amplitude of fictive gasping is decreased
• intracellular recordings of preBotzinger complex inspiratory neurons show that under control conditions, the depolarization in phase with the network burst is reduced in mutants and the number and frequency of action potentials per burst and firing frequency is lower
• upon transition from control to hypoxic conditions, mutants have a severe reduction of the underlying depolarization when challenged by hypoxia, the number and frequency of action potentials per burst drops dramatically compared to a mild reduction in controls

behavior/neurological

cardiovascular system
• lower heart rate, especially in late stages of disease

homeostasis/metabolism
• percentage of oxygen saturation of arterial blood in late-stage mutants is often less than 99% which is not seen in controls

immune system
• microglial activation is rarely seen in respiratory centers such as the medial parabrachial nucleus, nucleus of the solitary tract or preBotzinger complex, however it is seen in late-stage mutants around serotonergic cell bodies in the medullary raphe

integument
• mutants lose most of their hair at around P20

muscle

hematopoietic system
• microglial activation is rarely seen in respiratory centers such as the medial parabrachial nucleus, nucleus of the solitary tract or preBotzinger complex, however it is seen in late-stage mutants around serotonergic cell bodies in the medullary raphe

Mouse Models of Human Disease
OMIM IDRef(s)
Leigh Syndrome; LS 256000 J:190475


Mouse Genome Informatics
cn10
    Tg(ACTB-NOTCH1)1Shn/0
Tg(Nes-cre)1Kln/0

B6.Cg-Tg(Nes-cre)1Kln Tg(ACTB-NOTCH1)1Shn
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• some of the mutants die before birth; however, most survive to the perinatal stage

nervous system
• at E10 the number of apoptotic cells in the forebrain-midbrain junction is increased
• by E11.5 apoptosis is more widespread in the telencephalon with about 30% of all cells being TUNEL positive
• at E12 - 13.5 the ventricular zone harboring neural progenitors is thinner
• at E12 - 13.5 the telencephalon is smaller compared to wild-type or single transgenic littermates
• at E12 - 13.5 all brain subregions are smaller compared to wild-type or single transgenic littermates
• at P0 the brain especially the cerebral cortex is much smaller in double transgenic mice compared to wild-type or single transgenic littermates
• the number of postmitotic neurons is decreased at E12 - 13.5 in the telencephalon and diencephalon

cellular
• at E10 the number of apoptotic cells in the forebrain-midbrain junction is increased
• by E11.5 apoptosis is more widespread in the telencephalon with about 30% of all cells being TUNEL positive


Mouse Genome Informatics
cn11
    Uba6tm1Whpr/Uba6tm1Whpr
Tg(Nes-cre)1Kln/0

B6.Cg-Uba6tm1Whpr Tg(Nes-cre)1Kln
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• half of mice die between P5 and P21
• a quarter of mice that survive to P21 die within 2 months
• however, lethality is partially rescued by making food more accessible

behavior/neurological
• absence of stomach content in several mice at death
• in a forced swim test, mice spend less time immobilized compared with wild-type mice
• with altered response to an aversive stimulus
• in the Y-maze test
• constitutive without an alteration in body temperature
• slightly better performance on a rotarod
• in a novel environment with a lack of habituation
• pronounced in the dark phase
• aversion to nesting
• mice prefer to explore an empty chamber rather than a stranger mouse

nervous system
N
• neuronal apoptosis at E14.5 and P5 is normal (J:198126)
• reduced density in the CA3 region and amygdala
• in the CA3 region as early as P5, the basolateral amygdala and piriform cortex
• however, the number of neurons is normal in the CA1, dentate gyrus, cortex and cerebellar regions

homeostasis/metabolism
N
• mice exhibit normal body temperature and constant respiratory exchange ratio throughout the diurnal cycle (J:198126)
• hypermetabolic

growth/size/body
• at birth and 11 weeks


Mouse Genome Informatics
cn12
    Sox2tm2Skn/Sox2tm4.1Skn
Tg(Nes-cre)1Kln/0

either: (involves: 129S/Sv * C57BL/6 * SJL) or (involves: 129S/Sv * C57BL/6 * DBA/2 * SJL)
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• most mice die by 4 weeks of age

nervous system
• brain cultures of P0 neurospheres in EGF exhibit reduced neural stem cells by the second and fourth passage compared to wild-type cultures that continue to proliferate
• neurospheres from P0 brain cultures in EGF die out by the fifth or sixth passage unlike wild-type cultures that continue to proliferate
• P0 brain cultures in EGF and bFGF adhere to the plate at early passages before becoming exhausted unlike similarly treated wild-type cultures that continue to proliferate
• defects in neural stem cell maintenance are accompanied by a strong decrease in neurosphere size
• P7 brain cultures are exhausted between the first and fourth passage unlike wild-type cultures that continue to proliferate
• brain cultures from E14.5 mice are more viable than later cultures but exhibit reduced proliferation compared with wild-type cultures
• however, treatment of P0 cultures with media from wild-type cultures restores proliferation
• from P0 hippocampal development is reduced compared to in wild-type mice
• moderately at P0
• prematurely interrupted at P0
• at P0, the number of GFAP/nestin+ cells in the dentate gyrus sub-granular layer is slightly decreased compared to in wild-type mice
• at P2, the number of GFAP/nestin+ cells in the dentate gyrus is strongly reduced compared to in wild-type mice
• the reduction in dentate gyrus cells is attributed to decreased proliferation and transient increase in apoptosis compared to in wild-type mice
• almost completely by P7
• the reduction in dentate gyrus cells is attributed to decreased proliferation and transient increase in apoptosis compared to in wild-type mice
• slightly at P0 and markedly at P7
• at P0, the posterior ventrolateral cortex is slightly reduced in size compared to in wild-type mice

cellular
• brain cultures of P0 neurospheres in EGF exhibit reduced neural stem cells by the second and fourth passage compared to wild-type cultures that continue to proliferate
• neurospheres from P0 brain cultures in EGF die out by the fifth or sixth passage unlike wild-type cultures that continue to proliferate
• P0 brain cultures in EGF and bFGF adhere to the plate at early passages before becoming exhausted unlike similarly treated wild-type cultures that continue to proliferate
• defects in neural stem cell maintenance are accompanied by a strong decrease in neurosphere size
• P7 brain cultures are exhausted between the first and fourth passage unlike wild-type cultures that continue to proliferate
• brain cultures from E14.5 mice are more viable than later cultures but exhibit reduced proliferation compared with wild-type cultures
• however, treatment of P0 cultures with media from wild-type cultures restores proliferation


Mouse Genome Informatics
cn13
    Abcb7tm1Mdf/Y
Tg(Nes-cre)1Kln/0

either: B6.Cg-Tg(Nes-cre)1Kln Abcb7tm1Mdf or (involves: 129S4/SvJae * 129S6/SvEvTac * C57BL/6 * SJL)
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• only 4.3% of pups rather than the expected 12.5% are found at P1 (J:106838)
• none are found at weaning (J:106838)

nervous system
N
• no gross brain abnormalities are detected (J:106838)


Mouse Genome Informatics
cn14
    Stat5atm2Mam/Stat5atm2Mam
Stat5btm1Mam/Stat5btm1Mam
Tg(Nes-cre)1Kln/0

involves: 129 * 129S6/SvEvTac * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
growth/size/body
• 150% and 200% in male and female mice, respectively of that measured in control mice at 22 weeks of age
• increase 2.5- and 3.5-fold in male and female mice, respectively at 22 weeks of age
• increase in both subcutaneous and visceral fat mass
• increase 40% and 20% in male and female mice, respectively at 22 weeks of age
• gain more weight than control littermates starting from 8 weeks of age
• more profound after 16 weeks of age
• weigh on the average 65% (males) and 60% (females) more at 26 weeks of age

behavior/neurological
• increased food intake in male at 16 weeks of age
• increased food intake in both male and female at 26 weeks of age

homeostasis/metabolism
• reduced cold tolerance at 26 weeks of age
• 8-fold at 22 weeks of age
• 4.5-fold at 22 weeks of age
• reduced oxygen consumption normalized to lean mass in male mice at 26 weeks of age
• at 22 weeks of age
• at 22 weeks of age

adipose tissue
• 150% and 200% in male and female mice, respectively of that measured in control mice at 22 weeks of age
• increase 2.5- and 3.5-fold in male and female mice, respectively at 22 weeks of age
• increase in both subcutaneous and visceral fat mass
• larger mean cross-sectional areas of adipocytes in inguinal, parametrial and mesenteric fat pads
• at least 2 fold increase in weight of all 5 fat pads (inguinal, parametrial, retroperitoneal, mesenteric and perirenal)


Mouse Genome Informatics
cn15
    Stat5btm1Mam/Stat5btm1Mam
Tg(Nes-cre)1Kln/0

involves: 129 * 129S6/SvEvTac * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
growth/size/body
• 150% and 200% in male and female mice, respectively of that measured in control mice at 22 weeks of age
• increase 2.5- and 3.5-fold in male and female mice, respectively at 22 weeks of age
• increase in both subcutaneous and visceral fat mass
• increase 40% and 20% in male and female mice, respectively at 22 weeks of age
• gain more weight than control littermates starting from 8 weeks of age
• more profound after 16 weeks of age
• weigh on the average 65% (males) and 60% (females) more at 26 weeks of age

behavior/neurological
• increased food intake in male at 16 weeks of age
• increased food intake in both male and female at 26 weeks of age

homeostasis/metabolism
• reduced cold tolerance at 26 weeks of age
• 8-fold at 22 weeks of age
• 4.5-fold at 22 weeks of age
• reduced oxygen consumption normalized to lean mass in male mice at 26 weeks of age
• at 22 weeks of age
• at 22 weeks of age

adipose tissue
• 150% and 200% in male and female mice, respectively of that measured in control mice at 22 weeks of age
• increase 2.5- and 3.5-fold in male and female mice, respectively at 22 weeks of age
• increase in both subcutaneous and visceral fat mass
• larger mean cross-sectional areas of adipocytes in inguinal, parametrial and mesenteric fat pads
• at least 2 fold increase in weight of all 5 fat pads (inguinal, parametrial, retroperitoneal, mesenteric and perirenal)


Mouse Genome Informatics
cn16
    Cfl1tm1.1Wit/Cfl1+
Dstntm1.1Wit/Dstntm1.1Wit
Tg(Nes-cre)1Kln/0

involves: 129 * BALB/cJ * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
normal phenotype
• mice are viable and phenotypically normal


Mouse Genome Informatics
cn17
    Socs3tm1Ayos/Socs3tm1Ayos
Tg(Nes-cre)1Kln/0

involves: 129 * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
adipose tissue
• on a high fat diet total fat weight and individual fat pad weights increase less in mutants compared to wild-type mice

behavior/neurological
• food intake is decreased on a high fat diet compared to wild-type mice on the same diet
• leptin treatment induces a greater decrease in food intake in mutants compared to wild-type mice

growth/size/body
• on a high fat diet mutants gain less weight
• treatment with leptin induces greater weight loss in mutants

homeostasis/metabolism
• after 22 weeks on a high fat diet plasma free fatty acid levels are significantly lower in mutants
• after 22 weeks on a high fat diet triglyceride levels are significantly lower in mutants
• glucose clearance is significantly faster in mutants compared to wild-type mice
• on a high fat diet mutants do not develop insulin resistance


Mouse Genome Informatics
cn18
    Abl1tm2.1Goff/Abl1tm2.1Goff
Abl2tm1Ajk/Abl2tm1Ajk
Tg(Nes-cre)1Kln/0

involves: 129 * C57BL/6 * C57BL/6J * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• recovered at a frequency (20.5%) slightly less than the expected Mendelian ratio at two weeks of age

nervous system
• reduced number of proliferating GCPs in the secondary fissure in the posterior cerebellum at P8
• loss of proliferating GCPs is concentrated in areas where the BM is disrupted
• normal proliferation of GCPs in the cerebella-derived culture
• scores of granule cell precursors (GCPs) abnormally protrude into the subarachnoid space between the midbrain and cerebellum at E17
• laminin-labeled basement membrane (BM) is fragmented at E15 and E17
• loss of the pial BM in the cerebellum starting from around P8
• reduced anterior-posterior extent of the mutant adult cerebellum
• basic laminar structure of the anterior cerebellum, encompassing lobules I-V, is completely lost
• obvious defects in the organization of anterior lobules I-V in P7 and P1 cerebella
• adjacent lobules, such as lobules VIII and IX, are fused
• patches of granule cells are randomly scattered throughout the white matter
• abnormal Bergmann glial network correlates with breaches of the BM in the cerebellum at P8
• highly disorganized radial glial processes, with some of their endfeet protruding into the meninges in the mutant cerebellum at E15
• loosely aligned Purkinje cells, with some abnormally distributing at the cerebellar surface at P1
• GCPs ectopically embed within the cortex at P1
• ectopic granule cell differentiation near the broken BM at P8
• many granule cells ectopias at the cerebellar surface in the posterior regions of adult cerebella and along the fusion lines of adjacent lobules
• normal extent of migration of granule cells and granule cell-glia interactions at P10 before the loss of the BM
• decreased depth of the fissures
• both the cerebellar vermis and the two lateral hemispheres lack clear fissures on the surface
• disappearance of lobules IV and V in the anterior vermis
• smaller cerebellum in adult mice

behavior/neurological
• take approximately twice as long to cross the elevated balance beam
• dramatic increase in the number of foot slips

cellular
• reduced number of proliferating GCPs in the secondary fissure in the posterior cerebellum at P8
• loss of proliferating GCPs is concentrated in areas where the BM is disrupted
• normal proliferation of GCPs in the cerebella-derived culture


Mouse Genome Informatics
cn19
    Tnfrsf11atm1.1Pngr/Tnfrsf11atm1.2Pngr
Tg(Nes-cre)1Kln/0

involves: 129 * C57BL/6 * C57BL/6NTac * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
• ovariectomized mice fail to exhibit a change in body temperature unlike similarly treated wild-type mice
• in female mice during the light phase
• mice injected with RANKL (Tnfsf11) or LPS fail to develop severe hyperthermia unlike similarly treated wild-type mice
• mice injected with RANKL (Tnfsf11) fail to exhibit an increase in prostagladin levels unlike similarly treated wild-type mice
• mice injected with RANKL (Tnfsf11) fail to develop severe hyperthermia and do not exhibit a change in diurnal activity unlike similarly treated wild-type mice
• mice injected with Il1b or TNF exhibit an impaired fever response and alterations in circadian activity compared with similarly treated wild-type mice
• mice injected with RANKL (Tnfsf11) fail to exhibit an increase in prostagladin levels unlike similarly treated wild-type mice

immune system
• mice injected with LPS fail to develop severe hyperthermia and do not exhibit a change in diurnal activity unlike similarly treated wild-type mice

behavior/neurological
• in female mice during the light phase


Mouse Genome Informatics
cn20
    Gnl3tm2.1Rylt/Gnl3tm2.1Rylt
Tg(Nes-cre)1Kln/0

involves: 129 * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging

respiratory system

nervous system
• decrease in cellularity starting at E12.5
• increase in gamma-H2AFX protein in cells expressing this protein at E12.5
• major defects in the cerebellar primordium at E14.5 and E16.5
• major defects at E14.5 and E16.5
• smaller midbrain and hindbrain tegmentum at E14.5 and E16.5
• smaller at E14.5 and E16.5
• major defects in the cortex at E14.5 and E16.5
• major defects in the ganglionic eminence at E14.5 and E16.5
• decrease in neuronal stem cell numbers in the neuroepithelium at E12.5
• at E14.5 and E16.5

embryogenesis
• decrease in cellularity starting at E12.5
• increase in gamma-H2AFX protein in cells expressing this protein at E12.5


Mouse Genome Informatics
cn21
    Ahi1tm1Jgg/Ahi1tm2.1Jgg
Tg(Nes-cre)1Kln/0

involves: 129 * C57BL/6 * FVB/N * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
N
• mice exhibit normal mortality through weaning (J:158019)

vision/eye
• at P19, dark-adapted electrical activity is absent unlike in wild-type mice

nervous system
N
• brain morphology is normal (J:158019)


Mouse Genome Informatics
cn22
    Brca2tm1Brn/Brca2tm1Brn
Ptch1tm1Mps/Ptch1+
Trp53tm1Tyj/Trp53+
Tg(Nes-cre)1Kln/0

involves: 129 * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• 100% of mice develop medulloblastoma beginning at 10 weeks


Mouse Genome Informatics
cn23
    Brca2tm1Brn/Brca2tm1Brn
Ptch1tm1Mps/Ptch1+
Trp53tm1Tyj/Trp53tm1Tyj
Tg(Nes-cre)1Kln/0

involves: 129 * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• 100% of mice develop medulloblastoma beginning at 5 weeks


Mouse Genome Informatics
cn24
    Mycntm1Psk/Mycntm1Psk
Tg(Nes-cre)1Kln/0

involves: 129 * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
growth/size/body
• decrease in head size can be detected at E12.5
• moderate growth retardation

nervous system
N
• neuronal precursor cell apoptosis is similar to controls (J:79489)
• progenitor cells display smaller nuclei
• in the cerebellar neuroepithelium, rhombic lip, and external granule cell layer at E12.5 and E17.5
• premature differentiation is seen both in vivo and in vitro
• striking reduction in proliferation in the central nervous system in general at E13
• only a very small fraction of cells in the interior of the cerebellum primordium are proliferating at E13
• significant decrease in the number of proliferating cells in the ventricular zone of the telencephalon at E13
• the cerebellar neuroepithelium appears thinner, displays breaks, and has a deficiency in progenitor cells
• the cerebellar neuroepithelium appears thinner
• many regions of the VZ are noticeably reduced in thickness
• at E17.5 in the lateral VZ neuroprogenitor cells are more rounded and more densely packed
• at 8 - 16 weeks of age mice display profound microencephaly
• decrease in brain size can be detected at E12.5
• total brain mass relative to total body weight is reduced 2 fold compared to controls
• the developing cerebral cortex is particularly small
• cerebellum appears disorganized
• at P20 in the rostral region all 3 layers are severely affected
• profound reduction in the progenitor cell pool in both the external granule cell layer and in the neuroepithelium
• at E12.5 a significant reduction in neuroprogenitor cell numbers is seen in the cerebellar neuroepithelium and rhombic lip and the interior differentiating zone is reduced in size
• at E17.5 a subset of rhombic lip neuroprogenitor cells are more rounded and more densely packed
• severe defects in foliation
• profound reduction in the progenitor cell pool
• decrease is more pronounced in the rostral region
• the most rostral portion of the EGL is absent
• granule cell density is reduced 3- to 6-fold
• at P20 total granule cell numbers are reduced about 30-fold
• fails to expand resulting in decreased area and decreased cell number
• the developing cerebellum is particularly small
• at P20 the absolute weight and percent of total brain weight of the cerebellum is reduced by 4- to 6-fold compared to controls

vision/eye

embryogenesis
• the cerebellar neuroepithelium appears thinner, displays breaks, and has a deficiency in progenitor cells
• the cerebellar neuroepithelium appears thinner

cellular
• progenitor cells display smaller nuclei
• in the cerebellar neuroepithelium, rhombic lip, and external granule cell layer at E12.5 and E17.5
• premature differentiation is seen both in vivo and in vitro
• striking reduction in proliferation in the central nervous system in general at E13
• only a very small fraction of cells in the interior of the cerebellum primordium are proliferating at E13
• significant decrease in the number of proliferating cells in the ventricular zone of the telencephalon at E13


Mouse Genome Informatics
cn25
    Shc1tm1Ravi/Shc1tm1Ravi
Tg(Nes-cre)1Kln/0

involves: 129 * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
growth/size/body
• body weight is less than controls at 25 days of age

nervous system
• brain weight is less than controls at 25 days of age


Mouse Genome Informatics
cn26
    Tg(EEF1A1-SHC1*)1Ravi/0
Tg(Nes-cre)1Kln/0

involves: 129 * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
growth/size/body
• at birth and during early postnatal development, there is a slight body weight difference
• the biggest differences occur at 21 days of age
• later in life males have bigger body weight differences than females

nervous system
• apoptosis among neural progenitors is increased during embryonic brain development
• apoptosis is noted in the frontal cortex at E12.5 and in the pons at E10.5 and E12.5
• apoptosis among neural progenitors is increased during embryonic brain development
• proliferation of neural progenitors is not changed so presumably there are less progenitor cells in the developing brain
• brain weight is less than controls from 2 days of age to 1 year in age
• the biggest differences occur at 21 days of age
• the stratium area is smaller at 2 days of age than controls and becomes even smaller at 21 days of age
• the entire thickness of the primary somatosensory cortex is reduced to less than 85% of controls
• layers II through IV are more dramatically affected (reduced by less 60% of controls in layer IV) than layers V-VI (reduced by 92% of controls)
• the cerebral cortex is thinner at 2 days of age than controls and becomes even thinner at 21 days of age
• at 2 days of age, the cerebral cortex is 58% smaller than controls which is more affected than other parts of the brain
• olfactory bulb is 82% of controls at 2 days of age
• the SVZ area is smaller at 2 days of age than controls and becomes even smaller at 21 days of age

cellular
• apoptosis among neural progenitors is increased during embryonic brain development
• apoptosis is noted in the frontal cortex at E12.5 and in the pons at E10.5 and E12.5
• apoptosis among neural progenitors is increased during embryonic brain development
• proliferation of neural progenitors is not changed so presumably there are less progenitor cells in the developing brain


Mouse Genome Informatics
cn27
    Gt(ROSA)26Sortm1(SNCA*A53T)Djmo/Gt(ROSA)26Sor+
Tg(Nes-cre)1Kln/0

involves: 129 * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
normal phenotype


Mouse Genome Informatics
cn28
    Gt(ROSA)26Sortm2(SNCA*119)Djmo/Gt(ROSA)26Sor+
Tg(Nes-cre)1Kln/0

involves: 129 * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
normal phenotype


Mouse Genome Informatics
cn29
    Ahi1tm1Xjl/Ahi1tm1Xjl
Tg(Nes-cre)1Kln/0

involves: 129 * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
N
• mice do not exhibit increased anxiety in an open field, dark/light box, or elevated plus maze (J:166236)
• at 7 to 9 months and 12 to 15 months, mice spend more time immobile in a forced swim test (FTS) or tail suspension test (TST) than wild-type mice
• mice exhibit less escape activity from a water tank compared with wild-type mice
• however, treatment with antidepressants improves mobility in FTS and TST


Mouse Genome Informatics
cn30
    Fbxw7tm1.1Axbe/Fbxw7tm1.1Axbe
Notch1tm1Agt/Notch1+
Tg(Nes-cre)1Kln/0

involves: 129 * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• the number of Map+ cells that differentiate in culture is increased while the number of Nes+ cells is decreased compared to in cultures from wild-type mice

cellular
• the number of Map+ cells that differentiate in culture is increased while the number of Nes+ cells is decreased compared to in cultures from wild-type mice


Mouse Genome Informatics
cn31
    Pdcd10tm1Wami/Pdcd10tm1Wami
Tg(Nes-cre)1Kln/0

involves: 129 * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
N
• mice exhibit normal Mendelian ratio after birth (J:171969)
• mice do not survive past P3
• fewer than expected mice are born

nervous system
• abnormal cytoarchitecture


Mouse Genome Informatics
cn32
    Ccdc88atm4.1Mat/Ccdc88atm4.1Mat
Tg(Nes-cre)1Kln/0

involves: 129 * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• no mice are successfully weaned
• start to die after P12 with none surviving past P29

growth/size/body
• starting at P5

behavior/neurological
• inactive

nervous system
• increase in the width of the layer of DCX-positive neurons at P15


Mouse Genome Informatics
cn33
    Ccdc88atm4.1Mat/Ccdc88a+
Tg(Nes-cre)1Kln/0

involves: 129 * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• not as severe as in homozygous mice


Mouse Genome Informatics
cn34
    Sp2tm1.1Htg/Sp2tm1.1Htg
Tg(Nes-cre)1Kln/0

involves: 129 * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• many mice die between 2 and 5 weeks after birth with few surviving into adulthood
• many mice die between 2 and 5 weeks after birth with few surviving into adulthood

nervous system
• severely disrupted neuronal and glial differentiation
• reduced proliferation of neural stem and neural progenitor cells in the subependymal zone and rostral migratory stream
• enlarged due to increased neuroblasts
• mild in some mice at P21
• reduced volume at P21
• reduced volume at P21
• reduced volume at P21

growth/size/body
• at P7 and P21

cellular
• increased M-phase of neural stem and neural progenitor cells in the subependymal zone and rostral migratory stream of postnatal mice
• shortened G2-M transition in neural stem and neural progenitor cells
• partial arrest in G2 and M phase in neural stem and neural progenitor cells
• reduced proportion of neural stem and neural progenitor cells in G1/G0
• however, S phase duration is normal
• severely disrupted neuronal and glial differentiation
• reduced proliferation of neural stem and neural progenitor cells in the subependymal zone and rostral migratory stream


Mouse Genome Informatics
cn35
    Sp2tm1.1Htg/Sp2+
Tg(Nes-cre)1Kln/0

involves: 129 * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• reduced proliferation of neural stem and neural progenitor cells in the subependymal zone and rostral migratory stream
• enlarged due to increased neuroblasts
• reduced volume at P21
• reduced volume at P21
• reduced volume at P21

growth/size/body
• at P7 and P21

cellular
• reduced proliferation of neural stem and neural progenitor cells in the subependymal zone and rostral migratory stream


Mouse Genome Informatics
cn36
    Asic1tm1.1Ccli/Asic1tm1.1Ccli
Tg(Nes-cre)1Kln/0

involves: 129 * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
N
• hippocampal long term potentiation is similar to controls (J:193892)
• absence of ASIC-like currents in nucleated patches isolated from interneurons in stratum oriens alveus

behavior/neurological
N
• spatial memory and learning are similar to controls (J:193892)


Mouse Genome Informatics
cn37
    Braftm2.1Urr/Braftm2.1Urr
Tg(Nes-cre)1Kln/0

involves: 129 * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype

Cerebellar abnormalities in Braftm2Urr/Braftm2Urr Tg(Nes-cre)1Kln/0 and Braftm2.1Urr/Braftm2.1Urr Tg(Nes-cre)1Kln/0 mice

mortality/aging
• mice begin to die around P17
• no mice survive beyond P28

nervous system
• in the dentate granule cell layer
• however, no increase in astrocytic differentiation is observed in the dentate gyrus
• expansion of the pool of proliferating hippocampal progenitor cells in the third postnatal week
• at P10 and P20
• reduced volume of the dentate granule cell layer
• reduced volume at P21 but not P12
• cytoarchitectonic alterations affecting all lobes at P21
• irregular positions in the flocculonodular lobe LX
• Purkinje cells appear elongated
• reduced and irregular arborization in the cerebellar molecular layer with more than 2 times lengthening of primary dendrite length
• in the flocculonodular lobe LX
• reduced and irregular arborization in the cerebellar molecular layer with more than 2 times lengthening of primary dendrite length
• reduced glomeruli size indicating that the synapses of the granule cells with mossy fiber and Golgi cells do not form correctly
• reduced length with less well demarcated and fuzzy border
• reduced length with less well demarcated and fuzzy border
• less well demarcated and fuzzy border
• ced length with less well demarcated and fuzzy border and disorganized glomeruli

behavior/neurological
• autoaggression (biting of their toes) in 13 of 15 mice
• impaired ability to walk and balance on a rod
• however, mice walk normally otherwise
• impaired ability to walk and balance on a rod
• however, mice walk normally otherwise

growth/size/body

cellular
• in the dentate granule cell layer
• however, no increase in astrocytic differentiation is observed in the dentate gyrus
• expansion of the pool of proliferating hippocampal progenitor cells in the third postnatal week


Mouse Genome Informatics
cn38
    Braftm2Urr/Braftm2Urr
Tg(Nes-cre)1Kln/0

involves: 129 * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype

Cerebellar abnormalities in Braftm2Urr/Braftm2Urr Tg(Nes-cre)1Kln/0 and Braftm2.1Urr/Braftm2.1Urr Tg(Nes-cre)1Kln/0 mice

mortality/aging
• mice begin to die around P17
• no mice survive beyond P28

nervous system
• in the dentate granule cell layer
• however, no increase in astrocytic differentiation is observed in the dentate gyrus
• expansion of the pool of proliferating hippocampal progenitor cells in the third postnatal week
• at P10 and P20
• reduced volume of the dentate granule cell layer
• reduced volume at P21 but not P12
• cytoarchitectonic alterations affecting all lobes at P21
• irregular positions in the flocculonodular lobe LX
• Purkinje cells appear elongated
• reduced and irregular arborization in the cerebellar molecular layer with more than 2 times lengthening of primary dendrite length
• in the flocculonodular lobe LX
• reduced and irregular arborization in the cerebellar molecular layer with more than 2 times lengthening of primary dendrite length
• reduced glomeruli size indicating that the synapses of the granule cells with mossy fiber and Golgi cells do not form correctly
• reduced length with less well demarcated and fuzzy border
• reduced length with less well demarcated and fuzzy border
• less well demarcated and fuzzy border
• ced length with less well demarcated and fuzzy border and disorganized glomeruli

behavior/neurological
• autoaggression (biting of their toes) in 13 of 15 mice
• impaired ability to walk and balance on a rod
• however, mice walk normally otherwise
• impaired ability to walk and balance on a rod
• however, mice walk normally otherwise

growth/size/body

cellular
• in the dentate granule cell layer
• however, no increase in astrocytic differentiation is observed in the dentate gyrus
• expansion of the pool of proliferating hippocampal progenitor cells in the third postnatal week


Mouse Genome Informatics
cn39
    Hsd17b4tm2Baes/Hsd17b4tm2Baes
Tg(Nes-cre)1Kln/0

involves: 129 * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• mice are euthanized beyond 12 months due to severe coordination defects
• however, most mice survive to at least 1 year of age

reproductive system
• fewer and smaller litters than control mice (J:201698)
• from female mice (J:201698)
(J:201698)

nervous system
• minor at 6 months
• cerebella atrophy
• neuronal death after 6 months
• at 12 months of age
• loss of axonal integrity with swelling prior to demyelination
• myelin loss between 4 and 6 months in cerebellar branches, worsen at 10 to 12 months
• however, myelination in the central white matter is normal

behavior/neurological
• anxious phenotype beyond 12 weeks
• beyond 12 weeks
• beyond 12 weeks
• severe at 12 months
• on a rotarod from 4 weeks, worsening with age
• from 12 weeks of age, mice exhibit frequent falls
• unsteady gait beyond 12 weeks, worsening by 6 months
• mice exhibit poor fore limb hind limb coordination with ipsilateral paw placement
• with increased stance at 6 months

homeostasis/metabolism
• accumulation of long chain fatty acids in the cerebellum and cortex

growth/size/body
• at P7, P21 and beyond
• pre- and post-weaning

hematopoietic system
• minor at 6 months

immune system
• minor at 6 months


Mouse Genome Informatics
cn40
    Deaf1tm1.1Mico/Deaf1tm1.1Mico
Tg(Nes-cre)1Kln/0

involves: 129 * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
N
• learn to find a visible platform in a Morris water maze with efficiency equivalent to controls (J:211699)
• reduced freezing behavior in response to foot shock (J:211699)
• significantly reduced contextual fear memory 24 hours after first test (similar result with heterozygotes) (J:211699)
• find a submerged platform moved to the opposite quadrant faster than controls when retested 48 hours after first exposure, but only on first trial (J:211699)
• subsequent trials and trials 7 days later are like controls (J:211699)


Mouse Genome Informatics
cn41
    Itgb8tm1Lfr/Itgb8tm2Lfr
Tg(Nes-cre)1Kln/0

involves: 129/Sv * 129X1/SvJ * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cardiovascular system
• blood vessels in the brain do not run parallel to the astroglia
• vessels in the brain develop large irregular endothelial cell clusters
• at P0 hemorrhages are seen in the dorsal cortex, thalamus, and in the ganglionic eminence near the deep mesencephalic nucleus; however hemorrhages are not seen in adult mutants and no cortical lamination defects are seen in adults
• hemorrhaging is less severe than in mice homozygous for Itgb8tm1Lfr

nervous system
• at P0 hemorrhages are seen in the dorsal cortex, thalamus, and in the ganglionic eminence near the deep mesencephalic nucleus; however hemorrhages are not seen in adult mutants and no cortical lamination defects are seen in adults
• hemorrhaging is less severe than in mice homozygous for Itgb8tm1Lfr
• at E14.5 radial glia near the ganglionic eminence (where hemorrhaging could be seen) are disorganized but those in the developing cortex (where hemorrhages are not yet present) appear normal
• at P0 astroglia appear disorganized and lack the normal parallel organization
• blood vessels in the brain do not run parallel to the astoglia


Mouse Genome Informatics
cn42
    Rettm1Kln/Rettm1Kln
Tg(Nes-cre)1Kln/0

involves: 129/Sv * BALB/c * C57BL/6 * CBA/J * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• mutants have peroneal nerves (PN) of reduced length (~40% of control) at E11.5 and nerves are reduced in complexity at E12.5; diameter of peroneal nerve is also reduced
• phenotype at E12.5 is somewhat less severe than in Ret; Tg(Pgk1-cre)1Lni mice

limbs/digits/tail
• clubbed feet are observed in mutants after birth


Mouse Genome Informatics
cn43
    Lhx1tm1Tmj/Lhx1+
Rettm1Kln/Rettm1Kln
Tg(Nes-cre)1Kln/0

involves: 129/Sv * BALB/c * C57BL/6 * CBA/J * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• peroneal nerve at E12.5 is rerouted to the path of the tibial nerve
• trajectory of small branch emerging from PN in mutants does not match stereotyped path of dorsal growing PN axons in controls
• phenotype of mice is more severe than in wild-type Lhx1 background

cellular
• peroneal nerve at E12.5 is rerouted to the path of the tibial nerve
• trajectory of small branch emerging from PN in mutants does not match stereotyped path of dorsal growing PN axons in controls
• phenotype of mice is more severe than in wild-type Lhx1 background


Mouse Genome Informatics
cn44
    Bhlhe22tm2.1Meg/Bhlhe22tm2.1Meg
Tg(Nes-cre)1Kln/0

involves: 129/Sv * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
• resulting in skin lesions in most animals

integument
• animals display self-inflicted skin lesions


Mouse Genome Informatics
cn45
    Ndufs4tm1Rpa/Ndufs4tm1Rpa
Tg(Nes-cre)1Kln/0

involves: 129/Sv * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• mice die between P35 and P50

nervous system
• seizures increase as disease progresses
• in some mice when handled
• in some mice
• vasculature in the vestibular nuclei and posterior cerebellum is increased compared to in wild-type mice
• at late stages, mice exhibit hemorrhages in the brainstem and occasionally the midbrain unlike in wild-type mice
• mice exhibit a higher frequency of hemorrhage in the midbrain, and of gliosis and spongiform lesions in the anterior cerebellum compared with Ndufs4tm1.1Rpa homozygotes
• more often than in Ndufs4tm1.1Rpa homozygotes
• mice exhibit a higher frequency of hemorrhage in the midbrain, and of gliosis and spongiform lesions in the anterior cerebellum compared with Ndufs4tm1.1Rpa homozygotes
• in some mice
• after P38, mice exhibit spongiform encephalpathy within the vestibular nuclei of the brainstem, inferior olive, fastigial nucleus, caudal cerebellar vermis (nodulus and uvula), and olfactory bulb unlike wild-type mice
• mice exhibit a higher frequency of hemorrhage in the midbrain, and of gliosis and spongiform lesions in the anterior cerebellum compared with Ndufs4tm1.1Rpa homozygotes

behavior/neurological
• mice are very submissive and rarely vocalize in response to stress unlike wild-type mice
• mice are docile and not easily provoked compared with wild-type mice
• at late stages, mice groom and scratch rarely unlike wild-type mice
• intermittent
• starting at P35, mice develop severe ataxia with splayed legs and become unresponsive to a firm nudge unlike wild-type mice
• ataxia worsens between P35 and P50
• after P21, mice exhibit deteriorating performance on a balance beam compared with wild-type mice
• starting at P35, mice become unstable, lose their balance, and fall over unlike wild-type mice
• mice are unable to maintain their balance after P40 unlike wild-type mice
• after P21, mice exhibit deteriorating performance on a balance beam compared with wild-type mice
• after P40, mice exhibit deteriorating performance on a rotarod compared with wild-type mice
• in a forced swim test after P21, some mice stall, corkscrew, swim upright, or swim poorly compared with wild-type mice
• mice are sometime prone or unable to remain in a sitting position unlike wild-type mice
• mice exhibit reduced nocturnal activity compared with wild-type mice
• after P21
• after P40
• after P21, mice exhibit lop-headed, kyphosis, splayed hindlimbs, retropulsion, circling, falling, and difficulty righting unlike wild-type mice
• mice exhibit a progressive deterioration of footprint gait compared with wild-type mice
• in some mice
• in some mice
• slow and awkward starting at P35
• mice are less responsive to handling, touch, and toe pinch than wild-type mice
• as mice age
• in some mice
• after P40
• after middle stage disease, mice exhibit reduced nest building behavior compared with wild-type mice
• handling, toe pinch, and other stress rarely elicits vocalization unlike similarly treated wild-type mice
• seizures increase as disease progresses
• in some mice when handled
• in some mice

vision/eye
• in some mice
• in some mice
• in some mice
• mice exhibit decreased visual acuity measured by Morris water maze, visual cliff test, and visual placing compared with wild-type mice

growth/size/body
• between P35 and P50

cardiovascular system
• vasculature in the vestibular nuclei and posterior cerebellum is increased compared to in wild-type mice
• at late stages, mice exhibit hemorrhages in the brainstem and occasionally the midbrain unlike in wild-type mice
• mice exhibit a higher frequency of hemorrhage in the midbrain, and of gliosis and spongiform lesions in the anterior cerebellum compared with Ndufs4tm1.1Rpa homozygotes
• more often than in Ndufs4tm1.1Rpa homozygotes
• measured by OxMouse

respiratory system
• as early as P14, mice exhibit intermittent breathing irregularities including hypo- and hyperventilation and gasping unlike wild-type mice
• intermittent as early as P14

cellular
• submitochondrial particles isolated from the liver exhibit little to no complex I activity unlike wild-type samples
• complex I-dependent oxygen consumption in brain tissue is reduced compared to in wild-type mice
• however, mice exhibit normal complex II and IV activity

skeleton

homeostasis/metabolism
• at P30, mice exhibit decreased resting body temperature with spontaneous hypothermia unlike wild-type mice

muscle
• mice exhibit deficient or marked resistance/freezing in either hindlimb unlike wild-type mice

hematopoietic system

immune system

integument
N
• unlike Ndufs4tm1.1Rpa homozygotes, the hair cycle is normal (J:161393)
• mice are less responsive to handling, touch, and toe pinch than wild-type mice

Mouse Models of Human Disease
OMIM IDRef(s)
Leigh Syndrome; LS 256000 J:161393


Mouse Genome Informatics
cn46
    Gmnntm1Tjm/Gmnntm1Tjm
Tg(Nes-cre)1Kln/0

involves: 129/Sv * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
N
• mice exhibit normal survival (J:171716)

reproductive system

nervous system
N
• mice exhibit normal neuroanatomy (J:171716)
• neuron stem cells exhibit normal proliferation and differentiation (J:171716)
• neurosphere cells exhibit normal DNA replication (J:171716)

behavior/neurological
N
• mice exhibit normal locomotion, feeding, avoidance behavior, and response to noxious stimuli (J:171716)


Mouse Genome Informatics
cn47
    Gmnntm1Tjm/Gmnn+
Tg(Nes-cre)1Kln/0

involves: 129/Sv * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
reproductive system
• slightly from male mice
• however, female mice produce normal litters


Mouse Genome Informatics
cn48
    Gli2tm1Alj/Gli2tm6Alj
Tg(Nes-cre)1Kln/0

involves: 129/Sv * C57BL/6 * SJL * Swiss Webster
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• foliation occurs to a greater extent, with the vermis having a more defined intercrural structure and thicker IGL than in Gli2;En1 conditional knockouts


Mouse Genome Informatics
cn49
    Fostm7Wag/Fostm7Wag
Tg(Nes-cre)1Kln/?

involves: 129P2/OlaHsd
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
• deficiencies in contextual fear response
• spatial learning anomalies were indicated in a Morris water test

nervous system
• in the CA1 and CA3 regions long term potentiation is reduced after a single tetanic stimulation but normal LTP after 4 stimuli


Mouse Genome Informatics
cn50
    Tbxa2rtm1Cof/Tbxa2rtm1.1Bhk
Tg(Nes-cre)1Kln/0

involves: 129P2/OlaHsd * 129S/SvEv * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
respiratory system
• mice exposed to ovalbumin and U-46619 fail to exhibit increased airway resistance unlike control mice
• however, mice exposed to increasing doses of thromboxane receptor agonist U-46619 exhibit dose-dependent increase in airway resistance


Mouse Genome Informatics
cn51
    Cdkn2ctm1Bbd/Cdkn2ctm1Bbd
Trp53tm1Brn/Trp53tm1Tyj
Tg(Nes-cre)1Kln/0

involves: 129P2/OlaHsd * 129S1/Sv * 129S2/SvPas * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• 4/4 of mice receiving 4 Gy radiation at P5 develop cerebellar tumors by 5 months of age

Mouse Models of Human Disease
OMIM IDRef(s)
Medulloblastoma; MDB 155255 J:102702


Mouse Genome Informatics
cn52
    Mettm1Cpo/Mettm1Sst
Tg(Nes-cre)1Kln/?

involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6 * CD-1 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
vision/eye
N
• no effect on retinal ganglion cell survival after optic nerve axotomy (J:173661)


Mouse Genome Informatics
cn53
    Braftm1Sva/Braftm1Sva
Raf1tm2Bacc/Raf1+
Tg(Nes-cre)1Kln/0

involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• most die before weaning

growth/size/body
• mice are smaller in the postnatal period than Braf conditional knockouts

nervous system
• deficiency of terminal axonal projections of parvalbumin-positive neurons toward the lateral motor pools of the spinal cord is seen compared to controls
• proprioceptive axons enter spinal cord normally, but few progress beyond intermediate zone
• at P12, number of Ret+ neurons in DRG is reduced; numbers of CGRG+ neurons are increased


Mouse Genome Informatics
cn54
    Braftm1Sva/Braftm1.1Sva
Raf1tm1Bacc/Raf1tm2Bacc
Tg(Nes-cre)1Kln/0

involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• no double conditional embryos are found live at E14-15, but can be isolated at E13

nervous system
• DRG neurons cultured with NGF for 5 days show impaired axon outgrowth
• sensory nerve trunks form normally, but distal arborization is reduced compared to controls
• at E13, Ret levels in DRGs are reduced

cellular
• DRG neurons cultured with NGF for 5 days show impaired axon outgrowth


Mouse Genome Informatics
cn55
    Braftm1Wds/Braftm1.1Wds
Raf1tm1Bacc/Raf1tm2Bacc
Tg(Nes-cre)1Kln/0

involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• no double conditional embryos are found live at E14-15, but can be isolated at E13

nervous system
• DRG neurons cultured with NGF for 5 days show impaired axon outgrowth
• sensory nerve trunks form normally, but distal arborization is reduced compared to controls
• at E13, Ret levels in DRGs are reduced

cellular
• DRG neurons cultured with NGF for 5 days show impaired axon outgrowth


Mouse Genome Informatics
cn56
    Mettm1Cpo/Mettm1Sst
Tg(Nes-cre)1Kln/0

involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• mice exhibit reduced motor axon arborization (length and number of branches) in the pectoralis minor muscle compared with wild-type mice
• at P2, endplates in the pectoralis minor exhibit increased partially or completely denervated synapses compared with wild-type endplates
• however, mice exhibit normal innervation of the pectoralis minor muscle at E15.5 and of the pectoralis major
• by P2 in the C8 and T1 region of the spinal cord with no further reduction in adult mice
• mice exhibit reduced motor axon arborization (length and number of branches) in the pectoralis minor muscle compared with wild-type mice
• at P2, endplates in the pectoralis minor exhibit increased partially or completely denervated synapses compared with wild-type endplates
• however, mice exhibit normal innervation of the pectoralis minor muscle at E15.5 and of the pectoralis major

behavior/neurological
• in a wire hang test but not a rotarod


Mouse Genome Informatics
cn57
    Pitx2tm1.1Dmm/Pitx2tm1.1Sac
Tg(Nes-cre)1Kln/0

involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• mammillothalamic tract fibers are truncated or severely diminished compared to in control mice
• PAX6+ cells at the principal mammillary tract-mammillothalamic tract bifurcation are reduced compared to in control mice
• however, mice exhibit intact principal mammillary and mammillotegmental projections


Mouse Genome Informatics
cn58
    Ddb1tm1Spg/Ddb1tm1Spg
Trp53tm1Tyj/Trp53tm1Tyj
Tg(Nes-cre)1Kln/0

involves: 129P2/OlaHsd * 129S2/SvPas * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• mutants do not survive for more than a day

nervous system
• ventricular zone (VZ) and subventricular zone (SVZ) are irregularly enlarged with many abnormal cells; cells show high frequency of mitotic figures, apoptosis and irregularly shaped nuclei

vision/eye
• loss of lens epithelium cells is rescued compared to Ddb1tm1Spg;Tg(Nes-cre)1Kln mice; however, cells have abnormally large or small nuclei with irregular shapes and sporadic apoptosis


Mouse Genome Informatics
cn59
    Trp53tm1Brn/Trp53tm1Tyj
Tg(Nes-cre)1Kln/0

involves: 129P2/OlaHsd * 129S2/SvPas * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• 2/5 (40%) of mice receiving 4 Gy radiation at P5 develop cerebellar tumors by 5 months of age


Mouse Genome Informatics
cn60
    Brca2tm1Brn/Brca2tm1Brn
Trp53tm1Tyj/Trp53+
Tg(Nes-cre)1Kln/0

involves: 129P2/OlaHsd * 129S2/SvPas * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• tumors exhibit a loss of heterozygosity at the Trp53 gene
• 72% of mice develop medulloblastoma beginning at 21 weeks

Mouse Models of Human Disease
OMIM IDRef(s)
Medulloblastoma; MDB 155255 J:144617


Mouse Genome Informatics
cn61
    Brca2tm1Brn/Brca2tm1Brn
Trp53tm1Tyj/Trp53tm1Tyj
Tg(Nes-cre)1Kln/0

involves: 129P2/OlaHsd * 129S2/SvPas * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• 87% of mice develop medulloblastoma beginning at 13 weeks

Mouse Models of Human Disease
OMIM IDRef(s)
Medulloblastoma; MDB 155255 J:144617


Mouse Genome Informatics
cn62
    Atrtm2Bal/Atrtm2Bal
Cdkn2atm2Brn/Cdkn2atm2Brn
Tg(Nes-cre)1Kln/0

involves: 129P2/OlaHsd * 129S2/SvPas * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• similar neuropathology to mutant mice wild-type for Cdkn2a


Mouse Genome Informatics
cn63
    Itgavtm2Hyn/Itgavtm2.1Hyn
Tg(Nes-cre)1Kln/0

involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6 * FVB * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• mice have to be euthanized by 8 months due to urinary dysfunction and bacterial bladder infection
• some mice die by 4 weeks of age
• mice have to be euthanized by 8 months due to urinary dysfunction and bacterial bladder infection

nervous system
N
• mice do not exhibit peripheral nerve abnormalities (J:94376)
• more frequent by 6 months
• vascular abnormalities are initiated in the developing ganglionic eminences of the forebrain
• cerebral blood vessels are tortuous and distended compared to in control mice
• microhemorrhage in the brain at 3 weeks
• at E14.5, mice develop small bilateral cerebral hemorrhages that become progressively more severe throughout embryogenesis unlike control mice
• less severe than in null mice
• microhemorrhage in the spinal cord at 3 weeks
• glial degeneration in the fasciculus gracilis white matter region
• vascular abnormalities are initiated in the developing ganglionic eminences of the forebrain
• in the fasciculus gracilis
• in the fasciculus gracilis
• in the spinal cord white matter

behavior/neurological
• by 2 to 3 weeks, some mice develop motor dysfunction
• by 2 to 3 months, all mice exhibit hind limb coordination defects
• mice exhibit involuntary tail wriggling
• on a rotarod
• mice partially drag hind limbs
• spastic paraparesis by 6 months
• rigid at 2 to 3 months
• rigid at 2 to 3 months
• mice exhibit toe-walking
• mice partially drag hind limbs
• more frequent by 6 months

cardiovascular system
• vascular abnormalities are initiated in the developing ganglionic eminences of the forebrain
• cerebral blood vessels are tortuous and distended compared to in control mice
• microhemorrhage in the brain at 3 weeks
• at E14.5, mice develop small bilateral cerebral hemorrhages that become progressively more severe throughout embryogenesis unlike control mice
• less severe than in null mice
• microhemorrhage in the spinal cord at 3 weeks

muscle
N
• mice do not develop hind limb muscular atrophy (J:94376)
• in hind limb muscles at 2 to 3 months

renal/urinary system
• mice have to be euthanized by 8 months due to urinary dysfunction and bacterial bladder infection

immune system
• mice have to be euthanized by 8 months due to urinary dysfunction and bacterial bladder infection


Mouse Genome Informatics
cn64
    Ftotm1.1Pzg/Ftotm1.1Pzg
Tg(Nes-cre)1Kln/0

involves: 129P2/OlaHsd * 129S4/SvJaeSor * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
growth/size/body

homeostasis/metabolism
• relative to lean mass, mice exhibit increased oxygen consumption and carbon dioxide production compared with wild-type mice
• relative to lean mass, mice exhibit increased oxygen consumption and carbon dioxide production compared with wild-type mice

behavior/neurological
• when normalized to lean mass

skeleton


Mouse Genome Informatics
cn65
    Plectm4Gwi/Plectm4.1Gwi
Tg(Nes-cre)1Kln/0

involves: 129P2/OlaHsd * BALB/cJ * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• in the sciatic nerve


Mouse Genome Informatics
cn66
    Efnb2tm4Kln/Efnb2tm4Kln
Tg(Nes-cre)1Kln/0

involves: 129P2/OlaHsd * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
N
• normal hippocampal architecture (J:87398)
• reduced long term depression


Mouse Genome Informatics
cn67
    Gjc1tm1Weil/Gjc1tm1Weil
Tg(Nes-cre)1Kln/0

involves: 129P2/OlaHsd * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
vision/eye
• cone bipolar cells are present in mutants but they are void of glycine, indicating that neurotransmitter coupling between ON bipolar cells and glycinergic AII amacrine cells is disrupted in mutants
• scotopic electroretinogram recordings in response to 20 msec white light flashes in dark-adapted mutants showed that b-wave amplitudes were smaller than in wild-type controls but a-waves did not differ, indicating a defect in the rod driven circuitry


Mouse Genome Informatics
cn68
    Gjc1tm1Kwi/Gjc1tm1Weil
Tg(Nes-cre)1Kln/0

involves: 129P2/OlaHsd * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
vision/eye
• scotopic electroretinogram recordings in response to 20 msec white light flashes in dark-adapted mutants showed that b-wave amplitudes were 40% smaller than in wild-type controls but a-waves did not differ, indicating a defect in the rod driven circuitry


Mouse Genome Informatics
cn69
    Mapk8ip3tm1Ysok/Mapk8ip3tm1Ysok
Tg(Nes-cre)1Kln/0

involves: 129P2/OlaHsd * C57BL/6 * C57BL/6J * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• despite being born in Mendelian ratios, fewer than expected mice are found at P0 and P1
• no mice are alive at P2

nervous system
• mice lack the telencephalic commissure


Mouse Genome Informatics
cn70
    Dab1tm1.1Mull/Dab1tm1.1Mull
Tg(Nes-cre)1Kln/0

involves: 129P2/OlaHsd * C57BL/6 * C57BL/6J * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• at E16.5, neuron layers is defective compared to in control mice
• the preplate fails to split unlike in control mice
• at E16.5, mice lack the marginal zone unlike control mice
• at E16.5

behavior/neurological

cellular
• at E16.5, neuron layers is defective compared to in control mice


Mouse Genome Informatics
cn71
    Tg(Nes-cre)1Kln/0
Zfp568tm1Ckjs/Zfp568tm1Ckjs

involves: 129P2/OlaHsd * C57BL/6 * C57BL/6J * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
N
• mice exhibit normal cortical layering and neuronal migration (J:192224)
• reduced average size of primary and secondary neurospheres grown from neural stem cells due to reduced proliferation
• reduced proliferation in subventricular zone but not in the dentate gyrus
• at birth but not in adult mice

behavior/neurological
N
• mice exhibit normal performance in a Morris water maze (J:192224)

cellular
• reduced average size of primary and secondary neurospheres grown from neural stem cells due to reduced proliferation
• reduced proliferation in subventricular zone but not in the dentate gyrus


Mouse Genome Informatics
cn72
    Pdha1tm1Ptl/Y
Tg(Nes-cre)1Kln/0

involves: 129P2/OlaHsd * C57BL/6 * FVB/N * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• mice die prenatally (J:94805)


Mouse Genome Informatics
cn73
    Pdha1tm1Ptl/Pdha1tm1Ptl
Tg(Nes-cre)1Kln/0

involves: 129P2/OlaHsd * C57BL/6 * FVB/N * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• 50% fewer than expected mice are born (J:94805)

nervous system
• at P35 (J:94805)
• white matter structures of the forebrain including the commissural anterior (pars anterior), lateral olfactory tract, and corpus callosum are smaller and underdeveloped (J:94805)
• small and underdeveloped (J:94805)
• the size of the cerebellar peduncles are smaller than in wild-type mice (J:94805)
• the nucleus caudatus/putamen exhibit irregular local heterotopias and fibers are less organized and of smaller diameter than in wild-type mice (J:94805)
• neurons within the nuclei paraventricularis and anterodorsalis are reduced in density and number compared to in wild-type mice (J:94805)
• the stria medullaris is smaller and has fewer fibers than in wild-type mice (J:94805)
• pyramidal cells are not arranged in a tight cellular layer as in wild-type mice (J:94805)
• the thickness of neocortex is reduced with irregularly distributed sites of disturbed cytoarchitecture compared to in wild-type mice (J:94805)
• some mice exhibit neurons clustered in local heterotopia or as single layers with a lower neuronal density in the surrounding areas unlike in wild-type mice (J:94805)
• neuropils appear to have fewer than expected fibers (J:94805)
• the lateral olfactory tract is smaller and underdeveloped (J:94805)
• the granule cell layer is reduced in an irregular pattern (J:94805)
• small with fewer fibers (J:94805)
• the cerebellar nuclei within the white matter exhibits local heterotopias and distributed neuropil (J:94805)
(J:94805)


Mouse Genome Informatics
cn74
    Cdc42tm1.1Rac/Cdc42tm1.1Rac
Tg(Nes-cre)1Kln/0

involves: 129P2/OlaHsd * C57BL/6 * FVB/N * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• mice die within 72 hours of birth

nervous system
• more than half of mice exhibit mild or moderate hemorrhage in the lateral ventricle of the brain
• decreased apical neuronal progenitor cell numbers in the cerebral cortex at E14.5 and E16.5
• at E14.5, only sporadic proliferating cells are located in the basal ventricular zone and subventricular zone compared with wild-type mice
• at E16.5, proliferating cells are displaced from the ventricular surface and are present randomly in the basal ventricular and subventricular zone compared with wild-type mice
• decreased cell number at E16.5
• decreased cell number at E16.5
• nuclei lose their apical-basal direction
• clustering of the ependymal cells
• lack of lining ependymal cells inside the third ventricle, aqueduct and spinal cord central canal
• more than half of mice exhibit mild or moderate hemorrhage in the lateral ventricle of the brain
• neuronal cells lining the lateral ventricle lack apical membrane domain
• lack of lining ependymal cells
• lack of lining ependymal cells
• slight increase in cell numbers with disruption of cell polarization at E14.5
• flattened surface with hypoplasia
• abnormal orientation at E16.5 indicating a folding problem
• lacking ventricular and sub-ventricular zones
• E18.5 glial cells exhibit a fried egg morphology in culture unlike wild-type cells
• collapse of the central canal and lack of differentiated ependymal cells

cellular
• at E14.5 and E16.5, radial glial cell nuclei exhibit impaired interkinetic nuclear migration compared to in wild-type cells
• decreased apical neuronal progenitor cell numbers in the cerebral cortex at E14.5 and E16.5
• at E14.5, only sporadic proliferating cells are located in the basal ventricular zone and subventricular zone compared with wild-type mice
• at E16.5, proliferating cells are displaced from the ventricular surface and are present randomly in the basal ventricular and subventricular zone compared with wild-type mice

behavior/neurological
• in neonates

cardiovascular system
• more than half of mice exhibit mild or moderate hemorrhage in the lateral ventricle of the brain

respiratory system
• in neonates


Mouse Genome Informatics
cn75
    Ugcgtm1Hjg/Ugcgtm1.1Hjg
Tg(Nes-cre)1Kln/0

involves: 129P2/OlaHsd * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• all mutants die by 24 days of age with a median age of lethality of 18 days

homeostasis/metabolism
• ceramide concentration in the brain is decreased about 1.7-fold at P0 and P15, but sphingomyelin levels are consistently increased after birth

behavior/neurological
• when placed on their ridge mutants take about 6 seconds to roll over compared to less than 0.5 seconds for control littermates
• mutants develop severe ataxia with a shuffling gait and strong equilibrium impairments
• mutants are unable to balance on a rotating rod
• shuffling gait

nervous system
• the dendritic tree shows decreased height and arborization in mutant cerebella
• in culture neurite length and the number of branching points are decreased for Purkinje cells from E15.5 mutant embryos
• surface area of the axon of the femoral nerve is increased
• myelin surface area of the femoral nerve is increased and in some mutants splitting of the myelin sheath is seen

growth/size/body
• body weight is similar to control littermates at birth, but after birth mutants gain less weight than their control littermates


Mouse Genome Informatics
cn76
    Mecp2tm1Bird/Y
Tg(Nes-cre)1Kln/0

involves: 129P2/OlaHsd * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
(J:67910)

behavior/neurological
(J:67910)
(J:67910)
• develop a stiff, uncoordinated gait (J:67910)

craniofacial
• frequently exhibit uneven wearing of the teeth (J:67910)

endocrine/exocrine glands
(J:67910)

growth/size/body
• frequently exhibit uneven wearing of the teeth (J:67910)

reproductive system
(J:67910)

Mouse Models of Human Disease
OMIM IDRef(s)
Rett Syndrome; RTT 312750 J:67910


Mouse Genome Informatics
cn77
    Ddb1tm1Spg/Ddb1tm1Spg
Tg(Nes-cre)1Kln/0

involves: 129P2/OlaHsd * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• newborn mice die within 24 hours

nervous system
• EGL of cerebellum (proliferative zone) is almost absent in mutants
• overall size of mutant brains is decreased at birth compared to wild-type
• the fourth (IV) ventricle is open to the brain surface and filled with blood
• nearly complete loss of cells in the ventricular (VZ) and subventricular zones (SVZ) of lateral ventricles
• lateral ventricles are dramatically enlarged
• the aqueduct of Sylvius is open to the brain surface and filled with blood
• remaining laminated layers show reduced cellularity and numerous red blood cells
• cortex is much thinner at E16.5 from excess cell death
• VZ and SVZ of olfactory bulb are missing
• much smaller than controls
• most dorsolateral cortical regions lack any vasculature; remaining vessels are dilated compared to control
• many blood vessels in cerebellum are dilated, but severe hemorrhage is only detected in rostrolateral tip
• bleeding is restricted to the forebrain mainly
• newborn mutants all exhibit severe hemorrhage within cerebral hemispheres and cerebellum
• newborn mutants all exhibit severe hemorrhage within cerebral hemispheres and cerebellum
• at E14.5, neuroprogenitor cells (NPC) show massive apoptotic death in SVZ and VZ, including pyknotic cells in ganglionic eminence; peak is at E15.5
• at E16.5, cavitations result from hypocellularity in VZ and SVZ

vision/eye
• at E15.5, many progenitor epithelial cells are apoptotic
• at E16.5. fewer epithelial cells are present in central pool or equatorial region, with pyknotic nuclei found in whole epithelium layer
• lenses are severely degenerated in newborn mutants
• lens has fewer cells; cells are abnormally shaped and disorganized
• lens is much less transparent than in controls

cardiovascular system
• cerebrovascular vessels are abnormally dilated and many rupture
• in newborn brains, there are ~12-fold fewer vessels compared to controls
• bleeding is restricted to the forebrain mainly
• newborn mutants all exhibit severe hemorrhage within cerebral hemispheres and cerebellum
• newborn mutants all exhibit severe hemorrhage within cerebral hemispheres and cerebellum

cellular
• at E15.5, many progenitor epithelial cells are apoptotic
• at E16.5. fewer epithelial cells are present in central pool or equatorial region, with pyknotic nuclei found in whole epithelium layer
• at E14.5, neuroprogenitor cells (NPC) show massive apoptotic death in SVZ and VZ, including pyknotic cells in ganglionic eminence; peak is at E15.5
• at E16.5, cavitations result from hypocellularity in VZ and SVZ


Mouse Genome Informatics
cn78
    Braftm1Wds/Braftm1.1Wds
Tg(Nes-cre)1Kln/0

involves: 129P2/OlaHsd * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• mice tend to die in third week postnatal, although some survive to P35

growth/size/body
• at P32, body weight is ~25% of littermates
• from P12-14 onwards, mice show severe growth retardation

endocrine/exocrine glands
• perivascular hypothalamic axonal innervation to anterior lobe is reduced
• anterior lobe of pituitary gland is markedly reduced in size compared to controls

behavior/neurological
N
• mice show normal nociceptive response in hotplate assay (J:121660)
• mice appear hyperactive

nervous system
N
• dorsal root ganglion neurons survive in mutants; lumbar-vertebral neuron counts at L4 and L5 are similar to wild-type (J:121660)
• perivascular hypothalamic axonal innervation to anterior lobe is reduced
• anterior lobe of pituitary gland is markedly reduced in size compared to controls
• disproportionate thinning of cortex is observed

homeostasis/metabolism
• mice display hypoglycemia with blood glucose levels ~70% below normal
• when separated from other mice, body temperature drops 5 degrees within 15 minutes
• level is elevated in pituitary relative to controls
• level of growth hormone is elevated in individual pituitary endocrine cells


Mouse Genome Informatics
cn79
    Braftm1Wds/Braftm1Wds
Raf1tm2Bacc/Raf1+
Tg(Nes-cre)1Kln/0

involves: 129P2/OlaHsd * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• most die before weaning

growth/size/body
• mice are smaller in the postnatal period than Braf conditional knockouts

nervous system
• deficiency of terminal axonal projections of parvalbumin-positive neurons toward the lateral motor pools of the spinal cord is seen compared to controls
• proprioceptive axons enter spinal cord normally, but few progress beyond intermediate zone
• at P12, number of Ret+ neurons in DRG is reduced; numbers of CGRG+ neurons are increased


Mouse Genome Informatics
cn80
    Braftm1Wds/Braf+
Raf1tm2Bacc/Raf1tm2Bacc
Tg(Nes-cre)1Kln/0

involves: 129P2/OlaHsd * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
normal phenotype
• mice show no phenotypic abnormalities at any stage


Mouse Genome Informatics
cn81
    Braftm1Sva/Braf+
Raf1tm2Bacc/Raf1tm2Bacc
Tg(Nes-cre)1Kln/0

involves: 129P2/OlaHsd * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
normal phenotype
• mice show no phenotypic abnormalities at any stage


Mouse Genome Informatics
cn82
    Dbx1tm1(DTA)Apie/Dbx1+
Tg(Nes-cre)1Kln/0

involves: 129P2/OlaHsd * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• differences in cortical cytoarchitecture were observed in both rostral and caudal level
• the mutant cortex did not show a typical Reeler phenotype
• strong decrease to a complete loss of Reelin expressing cells in the rostrocaudal axis of the telencephalic vesicles and of the olfactory bulb at E11.5 and E12.5
• no significant differences in Reelin expression in cortex of the wild-type and mutant at E14.5


Mouse Genome Informatics
cn83
    Txnrd1tm1Marc/Txnrd1tm1Marc
Tg(Nes-cre)1Kln/0

involves: 129P2/OlaHsd * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
N
• most regions of the brain including the olfactory bulb, subventricular zone and cerebral cortex are morphologically normal (J:133173)
• fissure formation in the anterior cerebellum is reduced
• only lobules VII to X form, while lobules I to VI are fused and unlaminated
• there is no distinction between the molecular, Purkinje cell and granular layers in the anterior portions of the cerebellar cortex
• however, lamination of the posterior cerebellar cortex is normal
• the dendritic trees of Purkinje cells, in the anterior more so than the posterior cerebellum, are less elaborate than in wild-type mice
• at weaning the cerebellum is one fourth of wild-type in size
• cell proliferation is 3 times lower than normal at P7 and 2 times lower than normal at P14
• cell density in the granular layer in the anterior end is reduced the posterior lobules are smaller
• however, apoptotic rates are normal
• glial cells in the anterior cerebellum are disoriented
• Bergmann glial fibers in the anterior cerebellum are shorter, disoriented and reduced in density compared to in wild-type mice