Progress on Theme 1: Animal Models to Advance the Study of Human Disease

Programs and Activities Highlights

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ORIP-Supported Research Highlights

  • A Constitutively Expressed Fluorescent Ubiquitination-Based Cell-Cycle Indicator (FUCCI) in Axolotls for Studying Tissue Regeneration
    Regulation of cell-cycle progression is essential for cell proliferation during regeneration post-injury. After appendage amputation, the axolotl, Ambystoma mexicanum, regenerates missing structures through an accumulation of proliferating cells known as the blastema. To study cell division during blastema growth, the authors generated a transgenic line of axolotls that ubiquitously expresses a bicistronic version of the fluorescent ubiquitination-based cell-cycle indicator. This new line of animals will be useful for studying cell-cycle dynamics using in situ endpoint assays and in vivo imaging in developing and regenerating animals.

  • Gene and Transgenics Nomenclature for the Laboratory Axolotl—Ambystoma mexicanum
    The axolotl, Ambystoma mexicanum, is widely used in biological research because of its remarkable capacity for regeneration. Recent advancements in genetic and molecular toolkits are greatly accelerating scientific research using the axolotl, especially regarding tissue regeneration. At this juncture, a critical need exists to establish gene and transgenic nomenclature to ensure uniformity in axolotl research. Here, the authors propose guidelines for unified, genetic nomenclature when working with the axolotl.

  • A Neutralizing Antibody Target in Early HIV-1 Infection Was Recapitulated in Rhesus Macaques Immunized with the Transmitted/Founder Envelope Sequence
    Envelope proteins (Envs) of HIV-1 likely contain features that drive neutralization breadth. Researchers immunized rhesus macaques of both sexes using Envs from HIV-1-infected human subjects who developed either high or low neutralizing antibody (nAb) levels. Several animals developed nAbs when immunized with the Env from the high-neutralizing individual. Investigators mapped the targets of vaccine-elicited nAbs to a distinct loop region of Env, which also was targeted by neutralizing monoclonal antibodies from the infected individual and immunized monkeys. This is a promising starting point to drive nAb breadth, an ultimate goal of vaccine-design efforts.

  • Chloride Channel Accessory 1 Gene Deficiency Causes Selective Loss of Mucus Production in a New Pig Model
    Chloride channel accessory 1 (CLCA1) is thought to be essential for the expression of MUC5AC, an inflammatory mucin, in response to type 2 cytokines. Investigators used a knockout pig model to demonstrate the loss of MUC5AC+ cells throughout the airway mucosa. Consistent effects were observed in the intestinal mucosa. These findings suggest that CLCA1 plays a role in controlling the expression of MUC5AC expression during mucus production. This work provides a new animal model that can be used for further studies of mucus production at respiratory and intestinal sites.

  • Suppression of Human and Simian Immunodeficiency Virus Replication with the CCR5-Specific Antibody Leronlimab in Two Species
    The prevalence of HIV drug resistance has increased in recent years, in large part because of the use of antiretroviral therapy by people with HIV. Researchers showed that injections of leronlimab—an anti-CCR5 antibody that blocks the binding of HIV to CCR5—suppressed HIV replication in five patients with HIV for more than 7 years. They also found that the average amount of virus in the blood of leronlimab-treated rhesus macaques was 10,000 times lower than in untreated animals. These findings suggest that leronlimab is a safe and effective anti-HIV therapeutic drug.

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Last updated: 11-29-2022