IMPC phenotypes (gene matching)
B6.129S2-Ltbp4Gt(U3Cre)1Vmel/VmelKieg
| Status | Available to order |
| EMMA ID | EM:00003 |
| International strain name | B6.129S2-Ltbp4Gt(U3Cre)1Vmel/VmelKieg |
| Alternative name | 3C7 |
| Strain type | Gene-trap |
| Allele/Transgene symbol | Ltbp4Gt(U3Cre)1Vmel |
| Gene/Transgene symbol | Ltbp4 |
Information from provider
| Provider | Harald von Melchner |
| Provider affiliation | University of Frankfurt Medical School |
| Genetic information | Use of a gene trap strategy, that selects for integrations into genes transiently induced during early mouse development, for disruption of the mouse homolog of the human LTBP4 gene. |
| Phenotypic information | Transforming growth factor-betas (TGF-betas) are multifunctional growth factors that are secreted as inactive (latent) precursors in large protein complexes. These complexes include the latency-associated propeptide (LAP) and a latent transforming growth factor-beta binding protein (LTBP). Four isoforms of LTBPs (LTBP-1 to LTBP-4) have been cloned and are believed to be structural components of connective tissue microfibrils and local regulators of TGF-beta tissue deposition and signaling. By using a gene trap strategy, that selects for integrations into genes transiently induced during early mouse development, we have disrupted the mouse homolog of the human LTBP4 gene. Mice homozygous for the disrupted allele develop severe pulmonary emphysema, cardiomyopathy, and colorectal cancer. These highly tissue-specific abnormalities are associated with profound defects in the elastic fiber structure and with a reduced deposition of TGF-beta in the extracellular space. As a consequence, epithelial cells have reduced levels of phosphorylated Smad2 proteins, over-express c-myc, and undergo uncontrolled proliferation. This phenotype supports the predicted dual role of LTBP-4 as a structural component of the extracellular matrix and as a local regulator of TGF-beta tissue deposition and signaling. |
| Breeding history | Backcrossed more than 10 generations to C57BL/6. |
| References |
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Information from EMMA
| Archiving centre | Karolinska Institutet, Stockholm, Sweden |
Disease and phenotype information
Orphanet associated rare diseases, based on orthologous gene matching
- Cutis laxa with severe pulmonary, gastrointestinal and urinary anomalies / Orphanet_221145
MGI phenotypes (allele matching)
- rectal prolapse / MGI
- abnormal colon morphology / MGI
- abnormal intestinal mucosa morphology / MGI
- intestinal ulcer / MGI
- enlarged spleen / MGI
- atelectasis / MGI
- overexpanded pulmonary alveoli / MGI
- respiratory distress / MGI
- emphysema / MGI
- abnormal pulmonary alveolus morphology / MGI
- colitis / MGI
- increased heart weight / MGI
- ventricular cardiomyopathy / MGI
- abnormal pulmonary elastic fiber morphology / MGI
- proctitis / MGI
- abnormal intestinal goblet cell morphology / MGI
- enlarged myocardial fiber / MGI
- abnormal large intestine crypts of Lieberkuhn morphology / MGI
- enlarged lung / MGI
- abnormal cell physiology / MGI
- dilated heart ventricle / MGI
- increased large intestine adenocarcinoma incidence / MGI
- increased lung compliance / MGI
- abnormal pulmonary alveolus wall morphology / MGI
- abnormal aorta morphology / MGI
- enlarged heart / MGI
- abnormal interventricular septum morphology / MGI
- abnormal lung morphology / MGI
- abnormal skin morphology / MGI
- abnormal aorta elastic fiber morphology / MGI
- abnormal heart left ventricle morphology / MGI
- mortality/aging / MGI
- abnormal pulmonary alveolar system morphology / MGI
- postnatal lethality, incomplete penetrance / MGI
- cardiomyopathy / MGI
- increased gastrointestinal tumor incidence / MGI
MGI phenotypes (gene matching)
- abnormal aorta morphology / MGI
- enlarged heart / MGI
- heart right ventricle hypertrophy / MGI
- abnormal interventricular septum morphology / MGI
- rectal prolapse / MGI
- abnormal colon morphology / MGI
- abnormal intestinal mucosa morphology / MGI
- intestinal ulcer / MGI
- enlarged spleen / MGI
- abnormal lung morphology / MGI
- atelectasis / MGI
- overexpanded pulmonary alveoli / MGI
- thin dermal layer / MGI
- decreased body weight / MGI
- decreased body size / MGI
- abnormal cardiovascular system physiology / MGI
- respiratory distress / MGI
- emphysema / MGI
- abnormal skin morphology / MGI
- abnormal respiratory system physiology / MGI
- abnormal pulmonary alveolus morphology / MGI
- impaired skin barrier function / MGI
- colitis / MGI
- increased heart weight / MGI
- ventricular cardiomyopathy / MGI
- thick ventricular wall / MGI
- abnormal pulmonary elastic fiber morphology / MGI
- abnormal aorta elastic fiber morphology / MGI
- proctitis / MGI
- abnormal intestinal goblet cell morphology / MGI
- abnormal heart right ventricle morphology / MGI
- abnormal heart left ventricle morphology / MGI
- enlarged myocardial fiber / MGI
- abnormal large intestine crypts of Lieberkuhn morphology / MGI
- enlarged lung / MGI
- cardiomyopathy / MGI
- abnormal cell physiology / MGI
- dilated heart ventricle / MGI
- increased large intestine adenocarcinoma incidence / MGI
- increased gastrointestinal tumor incidence / MGI
- mortality/aging / MGI
- increased lung compliance / MGI
- abnormal pulmonary alveolar system morphology / MGI
- abnormal pulmonary alveolus wall morphology / MGI
- increased aorta wall thickness / MGI
- postnatal lethality, incomplete penetrance / MGI
Literature references
- Disruption of the gene encoding the latent transforming growth factor-beta binding protein 4 (LTBP-4) causes abnormal lung development, cardiomyopathy, and colorectal cancer.;Sterner-Kock Anja, Thorey Irmgard S, Koli Katri, Wempe Frank, Otte Jürgen, Bangsow Thorsten, Kuhlmeier Katharina, Kirchner Thomas, Jin Shenchu, Keski-Oja Jorma, von Melchner Harald, ;2002;Genes & development;16;2264-73; 12208849