Methods for reducing or shutting down lactation in non-human mammals and reagents therefor

A non-human mammal, lactation technology, applied in the fields of biochemical equipment and methods, chemical instruments and methods, animal/human proteins, etc.

Pending Publication Date: 2020-09-18
加尔文医学研究所 +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although the incidence of mastitis can be reduced by using, for example, pre-milk te

Method used

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  • Methods for reducing or shutting down lactation in non-human mammals and reagents therefor
  • Methods for reducing or shutting down lactation in non-human mammals and reagents therefor
  • Methods for reducing or shutting down lactation in non-human mammals and reagents therefor

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0132] Example 1. Mutant mouse line that produces lactation failure

[0133] 1. Generation of OAS2 mutant mouse line

[0134] Using N-ethyl-N-nitrosourea (ENU) mutagenesis and screening for lactation failure, a mouse line was established, in which heterozygous (wt / mt) female mice showed partial penetrance of poor lactation. Produce litters that cannot thrive ( figure 1 ), and homozygous (mt / mt) female mice experience complete failure of lactation ( figure 1 ), provides a dominant inheritance model.

[0135] 1.1 Mice

[0136] All mice were raised in the Australian Phenomics Facility and Garvan Institute under specific pathogen-free conditions, and all animal procedures were passed through the Australian National University or Gavin / Approved by Garvan / St Vincent's Animal Ethics and Experimentation Committees. All animals were fed and drank ad libitum, and were reared in a 12-hour day / night cycle at 22°C and 80% relative humidity.

[0137] ENU mutagenesis and lineage construction wer...

Embodiment 2

[0157] Example 2. Characterization of OAS2 mutant mouse line

[0158] 2.1 Method

[0159] 2.1.1 Histopathology and organ pathology analysis

[0160] A complete analysis of histology and pathology of the Jersey strain was carried out by the Australian Phenotypic Network (APN) Histopathology and Organ Pathology Service Center of the University of Melbourne. Macroscopic and microscopic examinations of female sib pairs at eight and 31 weeks composed of mt / mt and wt / wt siblings. For breast tissue, ovary, fallopian tube, bicornuate uterus, cervix, bladder, liver / gallbladder, cecum, colon, spleen / pancreas, mesenteric lymph nodes, stomach, duodenum, jejunum, ileum, kidney / adrenal glands, salivary glands / lymph nodes , Thymus, lung, heart, skin, eyes, brain, spinal cord, skeletal muscle, skeletal tissue / hind limbs for macro and micro examination.

[0161] 2.1.2 Expression in OAS2 mutant mouse milk protein

[0162] Quantitative PCR was performed on the mRNA of milk protein expressed in the ...

Embodiment 3

[0196] Example 3. Infusion of poly(I:C) into the breast of lactating mice

[0197] In this example, the inventors demonstrated that poly(I:C) (a representative OAS2 activator) can reduce or stop lactation when administered to lactating mice via intramammary infusion. The results showed that the administration of poly(I:C) resulted in lactation failure, premature degeneration, and mammary alveolar remodeling, so that the mammary glands infused in the previous pregnancy could recover and become fully capable of lactating after subsequent pregnancy.

[0198] 3.1 Method

[0199] Dilute the poly(I:C) stock solution with a concentration of 10 mg / ml in sterile saline according to the manufacturer's instructions, and then heat to 50°C. From this stock solution, the treatment and control solutions for injection into mouse mammary glands were prepared as follows:

[0200] Table 3: Injection master mix of 25ng / μl poly(I:C)

[0201]

[0202]

[0203] Table 4: Injection master mix for vehicle con...

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Abstract

The disclosure relates generally to methods and reagents for reducing or shutting down lactation in a non-human mammalian subject. In particular, the disclosure relates to a method of reducing or shutting down lactation in a non-human mammalian subject by administering to the subject by intramammary infusion an agent which activate the OAS2 signalling pathway or induce expression of OAS2. In someexamples, the methods and reagents of the disclosure may be useful for the prevention of mastistis in a non-human mammalian subject, such as a dairy cow.

Description

[0001] Cross references to related applications [0002] This application claims the priority of US Provisional No. 62 / 557,280 filed on September 12, 2017, the entire content of which is incorporated herein by reference in its entirety. Technical field [0003] The present disclosure generally relates to methods and reagents for reducing or shutting down lactation in non-human mammalian subjects. Specifically, the present disclosure relates to a method for reducing or shutting down lactation by administering an agent that activates the OAS2 signaling pathway or induces OAS2 expression to the subject by intramammary infusion in a non-human mammalian subject. In some examples, the methods and reagents of the present disclosure can be used to prevent mastitis in non-human mammalian subjects. Background technique [0004] Mastitis (inflammation of the breast or breast) is a common serious problem, especially in the dairy industry. Susceptibility to bovine mastitis may be caused by sev...

Claims

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Application Information

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IPC IPC(8): A61K31/713A61K31/739A61K31/787A61K38/16A61K39/102A61P15/14C12N9/12
CPCA61K31/713A61K39/02A61K38/164A61K31/739A61P15/14A61K31/787C12N9/1241C12Y207/07A61K2121/00C12N15/117C12N2310/17A61P31/04A61K2039/55561A61K2039/55544A61K2039/55572C12N15/01A61K39/39A61K2039/545A61K2039/57C07K14/555C07K14/7155A61K38/21A61K45/06
Inventor C·奥曼迪S·奥克斯N·霍斯曼
Owner 加尔文医学研究所
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