Overview

Also Known As:Id4^-

These Id4 knock-in/knock-out mice exhibit reduced brain size, impaired cell cycle transition in early neural stem cells, reduced body fat, resistance to high fat diet and impaired adipocyte differentiation. This strain may be useful for studying ID4 as a regulator of neurogenesis and adipogenesis.

Donating Investigator

Giles Duffield, University of Notre Dame

Genetic overview

Genetic Background	Generation

Id4^tm1Mais

Allele Type	Gene Symbol	Gene Name
Targeted (Reporter, Null/Knockout)	Id4	inhibitor of DNA binding 4

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Research Applications

Developmental Biology Research
Neurobiology Research
Research Tools
Endocrine Deficiency Research
Internal/Organ Research

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Details

Detailed Description

ID4 (inhibitor of DNA binding 4) is a transcriptional regulator containing a helix-loop-helix domain and lacking a DNA binding domain. Unique among the ID proteins, ID4 is involved in the regulation of neural stem cell differentiation and proliferation. The Id4 knockout/knockin allele has a GFP reporter and a PGK-neo cassette replacing exons 1-2 of the gene. Uniform GFP expression is observed in all cortical areas by E12.5. Mice homozygous for this null allele exhibit reduced brain size from E11.5, specifically a 30% reduction occurs in the ventricular surface of the telencephalon affecting dorsomedial progenitor zones. Impairment of G1-S cell cycle transition and premature differentiation in early neural stem cells results in reduced brain size in these mice. Like ID2, loss of ID4 affects adipogenesis. Homozygous mice have 50% less body fat weight and adipocyte size is reduced by half. Following 6 weeks on high fat diet, mice gain significantly less weight than wild-type littermates. This strain may be useful for studying ID4 as a regulator of neurogenesis and adipogenesis.

Development

A targeting vector containing the GFP (green fluorescent protein) coding regions and the neomycin resistance cassette was used to replace exons 1 and 2 through homologous recombination. The construct was electroporated into electroporated into 129X1/SvJ-derived JM-1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts. The resulting chimeric animals were crossed to C57BL/6 mice and then backcrossed to C57BL/6J in excess of 5 generations. Upon arrival at The Jackson Laboratory, mice were bred to C57BL/6J for at least 1 generation to establish the colony.

Expression Data

Expressed Gene	GFP, Green Fluorescent Protein,
Site of Expression	GFP is expressed in the brain.

Control Suggestions

Wild-type from the colony
000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

Yun K; Mantani A; Garel S; Rubenstein J; Israel MA. 2004. Id4 regulates neural progenitor proliferation and differentiation in vivo. Development 131(21):5441-8PubMed: 15469968 MGI: J:93574

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Genetics

Id4^tm1Mais

Allele Symbol: Id4^tm1Mais

Allele Name	targeted mutation 1, Mark A Israel
Allele Type	Targeted (Reporter, Null/Knockout)
Allele Synonym(s)	Id4^-; Id4^GFP
Gene Symbol and Name	Id4, inhibitor of DNA binding 4
Gene Synonym(s)
Expressed Gene	GFP, Green Fluorescent Protein,
Site of Expression	GFP is expressed in the brain.
Strain of Origin	129X1/SvJ
Chromosome	13
Molecular Note	GFP and a neomycin-resistance gene replaced exons 1 and 2 via homologous recombination. GFP expression was observed in the brain.

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Developmental Biology Research
- Internal/Organ Defects
  - brain
- Neurodevelopmental Defects
Neurobiology Research
- Fluorescent protein expression in neural tissue
- Cerebellar Defects
Research Tools
- Fluorescent Proteins
Endocrine Deficiency Research
- Adipose Defects
Internal/Organ Research
- Adipose Defects

Mammalian Phenotype Terms by Genotype

The following phenotype information is associated with a similar, but not exact match to this JAX^® Mice strain

Genotype: Id4^tm1Mais/Id4^tm1Mais
involves: 129X1/SvJ

cellular phenotype

abnormal neuron differentiation
- At E15.5, increase in proliferation of cells outside the ventricular zone (postmitotic region)
- cortical progenitor neurons differentiate precociously leading to an increased number of deep layer neurons at E15.5 and E18.5
- prolonged transition between G1 to S of neural stem cells in the ventricular zone

nervous system phenotype

abnormal neuron differentiation
- At E15.5, increase in proliferation of cells outside the ventricular zone (postmitotic region)
- prolonged transition between G1 to S of neural stem cells in the ventricular zone
- cortical progenitor neurons differentiate precociously leading to an increased number of deep layer neurons at E15.5 and E18.5

decreased brain size
- reduced size is apparent from E11.5 onwards

small lateral ventricles
- smaller lateral ventricles at E15.5 and E18.5

telencephalon hypoplasia
- reduced ventricular surface along the rostrocaudal axis at E15.5 and E18.5
- at E12.5, the ventricular surface was about 30% smaller along the mediolateral axis than in wild-type

abnormal hippocampus development
- approximately 50% reduction in hippocampal primodium

abnormal neocortex morphology
- thickening of the neocortex

abnormal telencephalon morphology

Genotype: Id4^tm1Mais/Id4^tm1Mais
involves: 129X1/SvJ * C57BL/6

behavior/neurological phenotype

hypoactivity
- mice have reduced activity on a running wheel

References

Yun K; Mantani A; Garel S; Rubenstein J; Israel MA. 2004. Id4 regulates neural progenitor proliferation and differentiation in vivo. Development 131(21):5441-8PubMed: 15469968 MGI: J:93574

Additional - Id4^tm1Mais related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Separated PCR:Id4
- Standard PCR:Generic Neo
- Probe:Generic Neo
- Genotyping resources and troubleshooting
Breeding Considerations

While maintaining a live colony, these mice are bred as heterozygotes. The Donating Investigator has not attempted to breed homozygotes. Heterozygote x heterozygote crosses produce fewer homozygotes than expected (14% vs. 25%).
- Additional Breeding and Husbandry Support
Mating System
- Wild-type x Heterozygote
- Heterozygote x Wild-type
Citation
When using the Id4^- mouse strain in a publication, please cite the originating article(s) and include MMRRC stock #41569 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

The Jackson Laboratory's Genotype Promise

The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.

Terms Of Use

General Terms and Conditions

See MMRRC for Additional Conditions of Distribution

Questions about Terms of Use

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

Also Known As:Id4-

Donating Investigator

Genetic overview

Research Applications

Detailed Description

Development

Expression Data

Control Suggestions

Additional Information

Selected References

Id4tm1Mais

Allele Symbol: Id4tm1Mais

Disease Terms

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Mammalian Phenotype Terms by Genotype

Genotype: Id4tm1Mais/Id4tm1Maisinvolves: 129X1/SvJ

cellular phenotype

nervous system phenotype

Genotype: Id4tm1Mais/Id4tm1Maisinvolves: 129X1/SvJ * C57BL/6

behavior/neurological phenotype

References

Additional - Id4tm1Mais related

Genotyping Protocols

Breeding Considerations

Mating System

Citation

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

The Jackson Laboratory's Genotype Promise

Terms Of Use

Licensing Information

Also Known As:Id4^-

Id4^tm1Mais

Allele Symbol: Id4^tm1Mais

Genotype: Id4^tm1Mais/Id4^tm1Mais
involves: 129X1/SvJ

Genotype: Id4^tm1Mais/Id4^tm1Mais
involves: 129X1/SvJ * C57BL/6

Additional - Id4^tm1Mais related