Lmbrd1, or limb region 1 (LMBR1) domain containing 1 gene, encodes a lysosomal membrane protein LMBD1. It is crucial for lysosomal release of vitamin B₁₂, participating in cobalamin coenzyme synthesis and thus involved in methionine synthase and methylmalonyl-coenzyme A mutase pathways [1,4]. This process is of great biological importance as it impacts various physiological functions related to vitamin B₁₂ metabolism. Genetic models, especially mouse models, are valuable for studying Lmbrd1's functions.

In Lmbrd1-deficient mice, complete loss of Lmbrd1 function leads to early embryonic death. The initiation of gastrulation is disturbed, while the initial formation of the proximal-distal axis remains unaffected [2]. In heterozygous knockout mice (Lmbrd1+/-), lack of Lmbrd1 results in increased cardiac-glucose uptake, cardiac hypertrophy, ventricular tissue fibrosis, elevated heart rate, and increased cardiac muscle contractility. As the mice age, there are signs of ventricular function deterioration, suggesting Lmbrd1 plays a role in cardiac energy homeostasis and function regulation [3].

In conclusion, Lmbrd1 is essential for the initiation of gastrulation during embryogenesis and for regulating cardiac function. The study of Lmbrd1 knockout mouse models has provided insights into its roles in these biological processes and potential implications in diseases related to embryonic development and cardiac function [2,3].

References:

1. Rutsch, Frank, Gailus, Susann, Suormala, Terttu, Fowler, Brian. 2010. LMBRD1: the gene for the cblF defect of vitamin B₁₂ metabolism. In Journal of inherited metabolic disease, 34, 121-6. doi:10.1007/s10545-010-9083-9. https://pubmed.ncbi.nlm.nih.gov/20446115/

2. Buers, Insa, Pennekamp, Petra, Nitschke, Yvonne, Skryabin, Boris V, Rutsch, Frank. 2016. Lmbrd1 expression is essential for the initiation of gastrulation. In Journal of cellular and molecular medicine, 20, 1523-33. doi:10.1111/jcmm.12844. https://pubmed.ncbi.nlm.nih.gov/27061115/

3. Tseng, Linda Tzu-Ling, Lin, Chieh-Liang, Pan, Kuei-Hsiang, Chang, Shin C, Chang, Ming-Fu. 2017. Single allele Lmbrd1 knockout results in cardiac hypertrophy. In Journal of the Formosan Medical Association = Taiwan yi zhi, 117, 471-479. doi:10.1016/j.jfma.2017.05.002. https://pubmed.ncbi.nlm.nih.gov/28549591/

4. Gailus, Susann, Suormala, Terttu, Malerczyk-Aktas, Ayse Gül, Hennermann, Julia B, Rutsch, Frank. 2010. A novel mutation in LMBRD1 causes the cblF defect of vitamin B(12) metabolism in a Turkish patient. In Journal of inherited metabolic disease, 33, 17-24. doi:10.1007/s10545-009-9032-7. https://pubmed.ncbi.nlm.nih.gov/20127417/